Inhibition of hairless protein mRNA

Abstract

Methods for inhibition of hairless protein mRNA using RNA interference is described, in particular methods for hair removal. Also described are nucleic acid constructs for RNAi-mediated inhibition of hairless protein mRNA and compositions including such constructs.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

This application is a continuation of U.S. application Ser. No. 11/113,423 filed Apr. 22, 2005, now abandoned which is based on U.S. Provisional Application Ser. No. 60/565,127 filed Apr. 23, 2004, the contents of each of which are incorporated by reference herein, and to each of which priority is claimed.

SEQUENCE LISTING

The specification further incorporates by reference a substitute Sequence Listing submitted via EFS on Jul. 2, 2007. Pursuant to 37 C.F.R. §1.52(e)(5), the substitute Sequence Listing text file, identified as 700503051.txt, is 2.0 Mb and was created on Jul. 2, 2007. The substitute Sequence Listing, electronically filed herewith, does not extend beyond the scope of the specification and thus does not contain new matter.

The sequence listing, submitted in duplicate on compact disk (CD), in lieu of a paper copy in compliance with 37 C.F.R. §§1.821(c) and 1.52(e), and in duplicate on CD (CRF copy), in compliance with 37 C.F.R. §1.821 (e) has been generated from the specification and figures and does not constitute new matter. The Sequence Listing has been prepared using FastSeq for Windows Version 4.0 software. Four identical CDs, labeled COPY 1, COPY 2, CRF of Sequence Listing submitted under 37 C.F.R. §1.821(e)—COPY 1 and CRF of Sequence Listing submitted under 37 C.F.R. §1.821(e)—COPY 2, (total four (4) CDs), created on Apr. 22, 2005 each contain file: “AP36462_SEQLIST.TXT”, of size 2.28 MB (2,398,842 bytes). The specification incorporates herein by reference, the CD copies of the Sequence Listing submitted under 37 C.F.R §§1.821(c) and 1.52(e). The sequence listing, submitted herein, does not extend beyond the scope of the specification, and thus, does not contain new matter.

BACKGROUND OF THE INVENTION

The following is a discussion of some relevant art relating to hairless protein, and to RNAi. This discussion is provided only to assist the understanding of the reader, and does not constitute an admission that any of the information provided or references cited constitutes prior art to the present invention.

As described in Christiano et al., PCT/US99/02128, WO 99/38965, The human hair follicle is a dynamic structure which generates hair through a complex and highly regulated cycle of growth and remodeling. Hardy, 1992, Trends Genet. 8:159; Rosenquist and Martin, 1996, Dev. Dynamics 205:379. Hair growth is typically described as having three distinct phases. In the first phase, knows as anagen, the follicle is generated and new hair grows.

During the second phase, known as catagen, the follicle enters the stage where elongation ceases and the follicle regresses because the matrix cells stop proliferating. At this stage, the lower, transient half of the follicle is eliminated due to terminal differentiation and keratinization, and programmed cell death. Rosenquist and Martin, 1996, Dev. Dynamics 205:379. Also during catagen, although the dermal papilla remains intact, it undergoes several remodeling events, including degradation of the extracellular matrix that is deposited during anagen. At the close of catagen, the hair is only loosely anchored in a matrix of keratin, with the dermal papilla located just below. The catagen stage occurs at a genetically predetermined time, which is specific for each hair type in a species.

The third phase, known as telogen, is characterized by the follicle entering a quiescent phase, during which the hair is usually shed. When a new hair cycle is initiated, it is thought that a signal from the dermal papilla stimulates the stem cells, which are thought to reside in the permanent portion of the follicle, to undergo a phase of downward proliferation and genesis of a new bulbous base containing matrix cells which then surround the dermal papilla. As the new anagen state progresses, these hair matrix cells produce a new hair, the cycle begins again. Each follicle appears to be under completely asynchronous control, resulting in a continuum of follicles in anagen, catagen, and telegen phases, leading to a relatively homogeneous hair distribution. Hardy, 1992, Trends Genet. 8:159; Rosenquist and Martin, 1996, Dev. Dynamics 205:379.

Christiano et al., PCT/US99/02128, WO 99/38965 describes isolated nucleic acid encoding human hairless protein, the isolated protein, and methods for identifying a compound that is capable of enhancing or inhibiting expression of a human hairless protein, and states that “A therapeutic approach using antisense to human hairless can be used to directly interfere with the translation of Human hairless protein messenger RNA into protein.” It further states that “antisense nucleic acid or ribozymes could be used to bind to the Human hairless protein mRNA or to cleave it.”

Thompson, U.S. Pat. No. 6,348,348, issued Feb. 19, 2002, describes human hairless gene and protein, and screening methods to identify agents that affect expression of the human hairless gene.

Christiano, U.S. patent application Ser. No. 10/122,013, publication 20030077614 (and corresponding Internation Application PCT/US02/11683, WO 02/083891), indicates that “The present invention provides DNAzymes and ribozymes that specifically cleave Hairless Protein mRNA.” The present invention also provides antisense oligonucleotides that specifically inhibit translation of Hairless Protein mRNA. (Abstract.) Also, it states that “This invention provides a nucleic acid molecule that specifically hybridizes to Hairless Protein mRNA so as to inhibit the translation thereof in a cell”; (Specification ¶ 0099) and that “Antisense oligodeoxynucleotides were synthesized as directed to the inhibition of Hairless expression based on the Hairless mRNA sequence.”

SUMMARY OF THE INVENTION

The present invention concerns the use of RNA interference (RNAi) to inhibit mRNA's involved in hair growth, resulting in inhibition of hair growth. For many applications, short interfering RNA (siRNA) are used. Thus, inhibition of hairless protein mRNA, particularly during catagen phase, can result in permanent or at least long term inhibition of hair growth, and thus provides a method for hair removal. Consequently, inhibition of hairless protein mRNA can be used for hair removal and/or hair growth inhibition in cosmetic, therapeutic, and industrial applications.

Thus, in a first aspect, the invention provides a method for hair removal from a mammal, e.g., a human. The method involves applying to a human in an area comprising hair follicles a double stranded nucleic acid molecule that includes a sequence of at least a portion of human hairless protein mRNA and a sequence complementary thereto.

In particular embodiments, the inhibition of hair growth in the treated area persists at least 1, 2, 4, 6, 8, 10, 12, or 24 months, or longer, or permanently.

In certain embodiments, the method also involves synchronizing hair growth cycles for hair follicles in the treated area, e.g., by extracting hairs such as by waxing. Such extraction causes follicles in anagen to transition into catagen thereby making those follicles susceptible to inhibition using this invention, and triggers new hair growth of follicles in telogen and thus makes those follicles suitable for transitioning into catagen. Thus, these methods synchronize hair follicles in the hair cycle.

As used in connection with this invention, the term “hair removal” refers to physical removal and continuing inhibition of hair growth from one or more hair follicles. Typically the hair removal applies to a plurality of hair follicles in a skin area on a subject. For example, the area can be up to 2, 5, 10, 20, 50, 100, 200, 400, or more cm². For hair removal in an area, the hair removal may apply to all or a fraction of the hair follicles in the area.

The term “hair follicle” is used conventionally to refer to a biological hair producing structure.

As used in connection with the present methods, the term “applying” indicates that a substance is placed such that the substance is physically present on or in an area.

The term “nucleic acid molecule” refers to a polymer that includes a plurality of linked nucleotides or nucleotide analogs, and may include one or more modified internucleotidic linkages.

The term “hairless gene” refers to a mammalian gene that corresponds to reference human cDNA GenBank reference number NM_—005144, FIG. 1 (SEQ ID NO: 11412) and version NM_—005144.3, GI:62750351, FIG. 2 (SEQ ID NO:11413), recognizing that polymorphisms and potentially sequencing errors may be present, or a species homolog of that sequence, e.g., mouse homolog cDNA sequence NM_—021877. Similarly the terms “hairless protein mRNA” and “hairless mRNA” refer to an mRNA encoding a hairless gene protein, and “human hairless mRNA” refers to a human homolog of such mRNA.

The phrase “inhibition of hair growth” is used to refer to a reduction or stoppage of hair growth caused at least in part by an agent not normally present in cells in a hair follicle.

As used herein, the phrase “synchronizing hair growth cycles” means that at least 10% of hair follicles in catagen or telogen phase in a particular area are caused to enter anagen phase essentially simultaneously (i.e., within 2 weeks). Such synchronizing can be accomplished, for example, with a physical action such as hair extraction or with one or more chemical or biomolecular agents.

As used herein, the term “hair extraction” refers to pulling of individual hair shafts out of their follicles.

A related aspect concerns a method for hair removal from an area of a mammal comprising hair follicles, where the method involves applying to the area a composition that includes at least one double stranded nucleic acid molecule able to inhibit hairless mRNA translation in vitro.

In certain embodiments, the method also includes synchronizing hair growth cycles for hair follicles in the treated area, such as by hair extraction, e.g., using waxing; the mammal is a human; the mammal is a mouse; the mammal is a rat; the mammal is a bovine.

In another aspect, the invention provides a method of inhibiting expression of hairless protein in a mammal. The method involves administering a double stranded nucleic acid molecule to the mammal, where the double stranded nucleic acid molecule includes a sequence selected from the group consisting of oligonucleotides 1-5664 and their respective antisense sequences, or the species homology of such sequences, and a sequence complementary thereto.

As used in the context of this invention, the term “inhibiting expression” indicates that the level of mRNA and/or corresponding protein or rate of production of the corresponding protein in a cell that would otherwise produce the mRNA and/or protein is reduced as compared to a non-inhibited but otherwise equivalent cell. Reduction in the rate of production can be at various levels, including stopping such production.

The term “species homolog” refers to a form of a gene, or corresponding nucleic acid molecule, or polypeptide from a particular species that is sufficiently similar in sequence to the gene, corresponding nucleic acid, or polypeptide from a reference species that one skilled in the art recognizes a common evolutionary origin.

Thus, as used in connection with a molecule or composition, the phrase “able to inhibit hairless mRNA translation” indicates that the molecule or composition has the property that when present in a cell that would translate hairless mRNA to produce protein in the absence of an inhibitor, the molecule or composition reduces the rate of biosynthesis of hairless protein (or even eliminate such biosynthesis). Such reduction can occur in various ways, for example, by reducing the amount of mRNA available for translation or by at least partially blocking translation of mRNA that is present.

Reference to Oligonucleotides by number utilizes the oligonucleotide numbering in Table 1, and therefore, specifies a nucleotide sequence.

In particular embodiments, the mammal is a human, a mouse, a rat, a bovine (such as a cow), an ovine (such as a sheep), a monkey, a porcine (such as domestic pig).

The term “bovine” is used conventionally to refer to cattle, oxen, and closely related ruminants.

Another aspect concerns a method for treating a human desirous of losing hair. The method involves administering to the human a composition that includes a double stranded nucleic acid molecule that includes a sequence of at least a portion of human hairless protein mRNA and a sequence complementary thereto.

As used herein, the phrase “desirous of losing hair” refers to an objective indication of consent or request for a process to remove hair from a body area in a manner reducing or eliminating future hair growth in that area for a period of time, e.g., at least 1 week, 2 weeks, 1 month, 2 months, or longer.

A further aspect concerns a method for marketing a composition for hair removal, which includes providing for sale to medical practitioners (e.g., doctors, nurse practitioners, doctor's assistants, and nurses) or to the public (e.g., spas and other body care businesses, and individuals) a packaged pharmaceutical composition that includes a double stranded nucleic acid molecule containing a sequence of at least a portion of human hairless protein mRNA and a sequence complementary thereto; and a package label or insert indicating that the pharmaceutical composition can be used for hair removal.

In particular embodiments, the pharmaceutical composition is approved by the U.S. Food and Drug Administration, and/or by an equivalent regulatory agency in Europe or Japan, for hair removal in humans; the pharmaceutical composition is packaged with a hair removal wax or other component adapted for hair removal.

The term “pharmaceutical composition” refers to a substance that contains at least one biologically active component. The composition typically also contains at least one pharmaceutically acceptable carrier or excipient.

As used herein, the term “packaged” means that the referenced material or composition is enclosed in a container or containers in a manner suitable for storage or transportation. For example, a pharmaceutical composition may be sealed in a vial, bottle, tube, or the like, which may itself be inside a box. Typically, a label on the container identifies the contents and may also provide instructions for use and/or cautions to prevent misuse.

The term “hair removal wax” refers to refer to a substance that is adapted for removal of hair by embedding hair in the substance and then pulling the material away, thereby pulling embedded hairs out of the hair follicles. The substance may be used with a backing material such as paper or cloth. Both hot and cold waxes are commonly available. Unless clearly indicated, the term is not limited to substances that are chemically waxes; for example, the term will generally include substances such as caramel-based substances that are used for “sugaring”.

The term “other component adapted for hair removal” refers to a material or device that can be used for physically removing hairs and is either generally recognized as suitable for such use, of instructions are provided indicating that the component can be used for physical hair removal or providing instructions on performing such removal.

Another aspect concerns an isolated double stranded nucleic acid molecule that includes a nucleotide sequence corresponding to 19-25 contiguous nucleotides from human hairless mRNA, where the nucleotide sequence contains a nucleotide sequence selected from the group consisting of oligonucleotides 1-5664; and a nucleotide sequence complementary thereto, where the double stranded nucleic acid molecule induces RNA interference in a human cell in vitro.

Indication that a molecule or material of interest “induces RNA interference in a human cell in vitro” means that when present in cultured cells that are capable of RNA interference and under conditions such that a molecule or molecules that will normally induce RNA interference do induce RNAi in the cell, the molecule or material of interest will induce such RNA interference.

Likewise, in another aspect the invention provides a pharmaceutical composition that includes a double stranded nucleic acid molecule that contains a nucleotide sequence corresponding to 14-50, 17-40, 17-30, 17-25, 19-30, 19-29, 19-28, 19-26, 19-25, 19-24, 19-23, 20-23, 20-22, or 21-22 contiguous nucleotides from human hairless mRNA including a nucleotide sequence selected from the group consisting of oligonucleotides 1-5664, and a sequence complementary thereto, wherein said double stranded nucleic acid molecule induces RNA interference in a human cell in vitro.

In yet another aspect, the invention provides a kit that includes a pharmaceutical composition that contains a double stranded nucleic acid molecule that includes a sequence of at least a portion of human hairless protein mRNA and a sequence complementary thereto; and a package label or insert indicating that said pharmaceutical composition can be used for hair removal.

In certain embodiments, the kit is approved by the U.S. Food and Drug Administration or equivalent regulatory agency in Europe or Japan, for human hair removal.

In certain embodiments of the above aspects or other aspects described herein, the double stranded nucleic acid includes at least one (i.e., one or two) 3′-overhang, e.g., a 1, 2, or 3 nucleotide overhang. In certain embodiments, such overhang includes one or more non-ribonucleotides; includes 1, 2, or 3 deoxynucleotide; includes a modified linkage; each strand has a 1, 2, or 3 nucleotide overhang.

In certain embodiments of the above aspects, at least one strand of the double stranded nucleic acid includes at least one nucleotide analog or internucleotidic linkage different from unmodified RNA; each strand includes at least one nucleotide analog or internucleotidic linkage different from unmodified RNA; at least one strand includes at least one modified nucleotide; each strand includes at least one modified nucleotide.

In certain embodiments of the above aspects, the double stranded nucleic acid molecule induces RNA interference in a cell in vitro and includes the RNA sense sequence of Oligonucleotide 131, namely 5′-CUCUCCAGACAUUUGGCAA-3′ (SEQ ID NO: 11329), and its complementary RNA sequence 5′-TTGCCAAATGTCTGGAGAG-3′ (SEQ ID NO:262); includes the RNA sense sequence of Oligonucleotide 1194, namely 5′-GUGCGGCCGAUCCGCGCCG-3′ (SEQ ID NO: 11330), and its complementary RNA sequence 5′-CGGCGCGGAUCGGCCGCAC-3′ (SEQ ID NO:11331); includes the RNA sense sequence of Oligonucleotide 1521, namely 5′-TGGGAGAAGACGGCCCCAG-3′ (SEQ ID NO:3041) its complementary RNA sequence 5′-CTGGGGCCGTCTTCTCCCA-3′ (SEQ ID NO: 3042); includes an RNA sense sequence and a complementary RNA antisense sequence selected from the group consisting of oligonucleotides 1-5664; is targeted to hairless mRNA corresponding to a site in the coding sequence (CDS) covering nucleotides 1482 to 5051; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1482 to 5032; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1482 to 4032; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1482 to 3032; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1482 to 2032; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1582 to 1732.

In certain embodiments of the above aspects, in the double stranded nucleic acid molecule, the sense sequence and the antisense sequence each include 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

In certain embodiments of the above aspects, chemically modified nucleic acids are used, e.g., chemically modified siRNAs (siNAs) as described in McSwiggen et al., PCT/US03/05346, WO 03/070918, which is incorporated herein by reference.

As used herein, the terms “siRNA” and “siNA” both refer to double stranded nucleic acid that induces RNAi, and includes unmodified RNA oligonucleotides and chemically modified oligonucleotides. When unmodified RNA is intended, the term “unmodified RNA” is expressly used.

The term “RNAi inducing oligonucleotide” or “RNA interference inducing oligonucleotide” refers to an oligonucleotide, generally a double stranded molecule (usually an siRNA molecule), that is able to induce RNA interference in a suitable cell.

In certain embodiments of the above aspects involving application of the present oligonucleotides to a mammal, the oligonucleotides are applied at 0.01 to 0.1 microgram/cm², 0.1 to 0.2 microgram/cm², 0.2 to 0.5 microgram/cm², 0.5 to 1.0 microgram/cm², 1.0 to 2.0 microgram/cm², 2.0 to 5.0 microgram/cm², or 5.0 to 10.0 microgram/cm²; a combination of different RNAi inducing oligonucleotides is applied, which application can be as a mixture or mixtures or separately, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or more different oligonucleotides; one or more different RNAi inducing oligonucleotides (e.g., all targeted to hairless, e.g., siRNA) is applied in combination (as a mixture or separately) with one or more different agents that inhibit hairless translation or hairless activity; one or more different RNAi inducing oligonucleotides is applied in combination with one or more other hair removal agents, such as chemical depilatories and/or enzymatic hair removal agents. In accordance with the preceding description of embodiments, certain of the present pharmaceutical compositions also include at least one hairless inhibiting agent different from an RNAi inducing agent, at least one chemical depilatory; at least one enzymatic hair removal agent.

In certain embodiments, the present RNAi inducing oligonucleotides are applied once; applied daily for at least 7 days; applied daily for at least 14 days; applied on at least 4 days within a one month period; applied on at least 7 days within a one month period; applied at least 4 days per week for at least a four week period.

In particular embodiments, the RNAi inducing oligonucleotide does not include the sequence of a siRNA as shown in the Examples; the RNAi oligonucleotide includes the sequence of an siRNA shown in the Examples and the method of use includes synchronizing hair cycles, e.g., as described herein.

In particular embodiments involving mammalian mRNAs, the RNAi inducing oligonucleotide (e.g., siRNA) includes a sequence 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length (or at least one of those lengths) of one of the sequences shown in Table 3, or a sequence complementary thereto; the RNAi inducing oligonucleotide targets a mammalian hairless mRNA sequence corresponding to a sequence shown in Table 3.

In particular embodiments, the RNAi inducing oligonucleotide (e.g., siRNA) targets a human hairless mRNA sequence as identified in Table 4; the RNAi inducing oligonucleotide contains a sequence of 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length (or at least one of those lengths).

In particular embodiments, the RNAi inducing oligonucleotide (e.g., siRNA) targets a mouse hairless mRNA sequence as identified in Table 5; the RNAi inducing oligonucleotide contains a sequence of 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length (or at least one of those lengths).

Additional embodiments will be apparent from the Detailed Description and from the claims.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1. NM005144 (SEQ ID NO:11412)

FIG. 2. NM005144.3 (SEQ ID NO: 11413)

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention concerns methods for inhibiting hair growth, by inhibiting particular mRNAs using RNAi, e.g., using siRNA. In particular non-limiting embodiments, the present invention provides for siRNA molecules, e.g., double stranded RNA oligonucleotides (which optionally may be chemically modified and/or comprise at least one 3′ overhang, as set forth below), comprising a nucleotide sequence that is complementary to a target nucleotide sequence which may be 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotides in length, where the siRNA contains a sequence 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 base pairs in length. Preferably, the hairless in RNA target nucleotide sequence comprises a 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotide portion of the human hairless mRNA sequence set forth in FIG. 1 (SEQ ID NO: 11412) and/or FIG. 2 (SEQ ID NO: 11413). Non-limiting examples of target sequences may be identified as loops identified in secondary mRNA structure using software designed for such purpose (e.g. RnaDraw, RnaMotif, Rnaview-RnaMLView, RnaViz, Vienna RNA Package, etc.).

A. RNAi and siRNA

RNA interference (RNAi) refers to the process of sequence-specific post-transcriptional gene silencing in animals mediated by short interfering RNAs (siRNAs) (Fire et al., 1998, Nature, 391, 806). The corresponding process in plants is commonly referred to as post-transcriptional gene silencing or RNA silencing and is also referred to as quelling in fungi. The process of post-transcriptional gene silencing is thought to be an evolutionarily-conserved cellular defense mechanism used to prevent the expression of foreign genes and is commonly shared by diverse flora and phyla (Fire et al., 1999, Trends Genet., 15, 358). The presence of dsRNA in cells triggers the RNAi response though a mechanism that appears to be different from the interferon response that results from dsRNA-mediated activation of protein kinase PKR and 2′,5′-oligoadenylate synthetase resulting in non-specific cleavage of mRNA by ribonuclease L.

The presence of long dsRNAs in cells stimulates the activity of the enzyme, dicer, a ribonuclease III. Dicer is involved in the processing of the dsRNA into short pieces of dsRNA known as short interfering RNAs (siRNAs) (Berstein et al., 2001, Nature, 409, 363). The resulting RNAs are typically about 21 to about 23 nucleotides in length, with complementary sequences of about 19 base pairs. Dicer has also been implicated in the excision of 21- and 22-nucleotide small temporal RNAs (stRNAs) from precursor RNA of conserved structure that are implicated in translational control (Hutvagner et al., 2001, Science, 293, 834). The RNAi response also involves an endonuclease complex, commonly referred to as an RNA-induced silencing complex (RISC), which mediates cleavage of single-stranded RNA having sequence complementary to the antisense strand of the siRNA duplex. Cleavage of the target RNA takes place in the middle of the region complementary to the antisense strand of the siRNA duplex (Elbashir et al., 2001, Genes Dev., 15, 188).

RNAi has been studied in a variety of systems. Fire et al., 1998, Nature, 391, 806, described RNAi in C. elegans. Wianny and Goetz, 1999, Nature Cell Biol., 2, 70, describe RNAi mediated by dsRNA in mouse embryos. Hammond et al., 2000, Nature, 404, 293, describe RNAi in Drosophila cells transfected with dsRNA. Elbashir et al., 2001, Nature, 411, 494, describe RNAi induced by introduction of duplexes of synthetic 21-nucleotide RNAs in cultured mammalian cells including human embryonic kidney and HeLa cells.

Work in Drosophila embryonic lysates (Elbashir et al., 2001, EMBO J, 20, 6877) has revealed certain factors of siRNA length, structure, chemical composition, and sequence that are significantly affect efficient RNAi activity. These studies have shown that 21-nucleotide siRNA duplexes are most active when containing 3′-terminal nucleotide overhangs. Furthermore, complete substitution of one or both siRNA strands with 2′-deoxy (2′-H) or 2′-O-methyl nucleotides abolishes RNAi activity, whereas substitution of the 3′-terminal siRNA overhang nucleotides with 2′-deoxy nucleotides (2′-H) was shown to be tolerated. Single mismatch sequences in the center of the siRNA duplex were also shown to abolish RNAi activity. In addition, these studies also indicate that the position of the cleavage site in the target RNA is defined by the 5′-end of the siRNA guide sequence rather than the 3′-end of the guide sequence (Elbashir et al., 2001, EMBO J., 20, 6877). Other studies have suggested that a 5′-phosphate on the target-complementary strand of a siRNA duplex is important for siRNA activity and that ATP is utilized to maintain the 5′-phosphate moiety on the siRNA (Nykanen et al., 2001, Cell, 107, 309).

Studies have shown that replacing the 3′-terminal nucleotide overhanging segments of a 21-mer siRNA duplex having two 2-nucleotide 3′-overhangs with deoxyribonucleotides does not have an adverse effect on RNAi activity. Replacing up to 4 nucleotides on each end of the siRNA with deoxyribonucleotides has been reported to be well-tolerated whereas complete substitution with deoxyribonucleotides results in no RNAi activity, but that substitution of siRNA with 2′-O-methyl nucleotides completely abolishes RNAi activity. (Elbashir et al., 2001, EMBO J., 20, 6877.)

Li et al., International PCT Publication No. WO 00/44914, and Beach et al., International PCT Publication No. WO 01/68836 both suggest that siRNA “may include modifications to either the phosphate-sugar backbone or the nucleoside . . . to include at least one of a nitrogen or sulfur heteroatom.”

Kreutzer and Limmer, Canadian Patent Application No. 2,359,180, also describe certain chemical modifications for use in dsRNA constructs in order to counteract activation of double-stranded RNA-dependent protein kinase PKR, specifically 2′-amino or 2′-O-methyl nucleotides, and nucleotides containing a 2′-O or 4′-C methylene bridge

Parrish et al., 2000, Molecular Cell, 6, 1977-1087, tested certain chemical modifications targeting the unc-22 gene in C. elegans using long (>25 nt) siRNA transcripts. The authors describe the introduction of thiophosphate residues into these siRNA transcripts by incorporating thiophosphate nucleotide analogs with T7 and T3 RNA polymerase and observed that “RNAs with two [phosphorothioate] modified bases also had substantial decreases in effectiveness as RNAi triggers (data not shown); [phosphorothioate] modification of more than two residues greatly destabilized the RNAs in vitro and we were not able to assay interference activities.” Id. at 1081. The authors also tested certain modifications at the 2′-position of the nucleotide sugar in the long siRNA transcripts and observed that substituting deoxynucleotides for ribonucleotides “produced a substantial decrease in interference activity,” especially in the case of Uridine to Thymidine and/or Cytidine to deoxy-Cytidine substitutions. Id. In addition, the authors tested certain base modifications, including substituting, in sense and antisense strands of the siRNA, 4-thiouracil, 5-bromouracil, 5-iodouracil, and 3-(aminoallyl)uracil for uracil, and inosine for guanosine. They found that whereas 4-thiouracil and 5-bromouracil were all well-tolerated, inosine “produced a substantial decrease in interference activity” when incorporated in either strand. Incorporation of 5-iodouracil and 3-(aminoallyl)uracil in the antisense strand resulted in substantial decrease in RNAi activity as well.

Beach et al., International PCT Publication No. WO 01/68836, describes specific methods for attenuating gene expression using endogenously-derived dsRNA.

Tuschl et al., International PCT Publication No. WO 01/75164, describe a Drosophila in vitro RNAi system and the use of specific siRNA molecules for certain functional genomic and certain therapeutic applications; although Tuschl, 2001, Chem. Biochem., 2, 239-245, doubts that RNAi can be used to cure genetic diseases or viral infection due “to the danger of activating interferon response.”

Li et al., International PCT Publication No. WO 00/44914, describe the use of specific dsRNAs for use in attenuating the expression of certain target genes.

Zernicka-Goetz et al., International PCT Publication No. WO 01/36646, describe certain methods for inhibiting the expression of particular genes in mammalian cells using certain dsRNA molecules.

Fire et al., International PCT Publication No. WO 99/32619, describe particular methods for introducing certain dsRNA molecules into cells for use in inhibiting gene expression.

Plaetinck et al., International PCT Publication No. WO 00/01846, describe certain methods for identifying specific genes responsible for conferring a particular phenotype in a cell using specific dsRNA molecules.

Mello et al., International PCT Publication No. WO 01/29058, describe the identification of specific genes involved in dsRNA-mediated RNAi.

Deschamps Depaillette et al., International PCT Publication No. WO 99/07409, describe specific compositions consisting of particular dsRNA molecules combined with certain anti-viral agents.

Waterhouse et al., International PCT Publication No. 99/53050, describe certain methods for decreasing the phenotypic expression of a nucleic acid in plant cells.

Driscoll et al., International PCT Publication No. WO 01/49844, describe specific DNA constructs for use in facilitating gene silencing in targeted organisms.

Parrish et al., 2000, Molecular Cell, 6, 1977-1087, describe specific chemically-modified siRNA constructs targeting the unc-22 gene of C. elegans.

Grossniklaus, International PCT Publication No. WO 01/38551, describes certain methods for regulating polycomb gene expression in plants.

Churikov et al., International PCT Publication No. WO 01/42443, describe certain methods for modifying genetic characteristics of an organism.

Cogoni et al., International PCT Publication No. WO 01/53475, describe certain methods for isolating a Neurospora silencing gene and uses thereof.

Reed et al., International PCT Publication No. WO 01/68836, describe certain methods for gene silencing in plants.

Honer et al., International PCT Publication No. WO 01/70944, describe certain methods of drug screening using transgenic nematodes as Parkinson's Disease models.

Deak et al., International PCT Publication No. WO 01/72774, describe certain Drosophila-derived gene products.

Arndt et al., International PCT Publication No. WO 01/92513, describe certain methods for mediating gene suppression by using factors that enhance RNAi.

Tuschl et al., International PCT Publication No. WO 02/44321, describe certain synthetic siRNA constructs.

Pachuk et al., International PCT Publication No. WO 00/63364, and Satishchandran et al., International PCT Publication No. WO 01/04313, describe certain methods and compositions for inhibiting the function of certain oligonucleotide sequences.

Echeverri et al., International PCT Publication No. WO 02/38805, describe certain C. elegans genes identified via RNAi.

Kreutzer et al., International PCT Publications Nos. WO 02/055692, WO 02/055693, and EP 1144623 B1 describes certain methods for inhibiting gene expression using RNAi.

Graham et al., International PCT Publications Nos. WO 99/49029 and WO 01/70949, and AU 4037501 describe certain vector expressed long double stranded RNA molecules.

McSwiggen et al., PCT/US03/05028, WO 03/074654 describes RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA), and provides a table listing thousands of mRNAs, which is believed to include hairless protein mRNA, as potential targets for such siNA.

McSwiggen et al., PCT/US03/05346, WO 03/070918 describes synthetic chemically modified small nucleic acid molecules capable of mediating RNA interference against target nucleic acid sequences. The reference reports that up to all of the nucleotides in the RNA strands can be replaced with moieties that are not ribonucleotides.

B. Hairless Protein mRNA

Applicant's have found that RNAi can be used to inhibit translation from hairless protein mRNA, resulting in hair removal. This hair removal is long term, or even permanent, thus providing cosmetic and therapeutic methods, as well as methods useful for laboratory experimental mammals, and for de-hairing in the leather industry.

The Hairless Protein gene is expressed during a narrow window during the hair cycle, just at the transition to catagen (the regression phase). (Panteleyev et al. 1998, Exp Dermatol. 7:249-67; Panteleyev et al. 2000, Am J Pathol. 157:1071-9). In both humans and mice with mutations in the hairless gene, the cardinal finding is a wave of hair shedding shortly after birth, and no subsequent hair growth throughout life. The phenotype results from permanent structural damage to the hair follicle, after which no further hair cycling can occur. In addition, humans and mice which are genetically deficient in hairless gene expression exhibit no other phenotypic manifestations or abnormalities that might be associated with a deleterious effect (Zlotogorski et al., 2002, J Invest Dermatol. 118:887-90), suggesting that hairless is specifically involved and indispensable in regulating the hair cycle, and that its functions elsewhere in the body (if any) are compensated by other factors.

As a result, hair removal using RNAi targeted to hairless mRNA provides an advantageous approach, as any inadvertent, non-localized inhibition of hairless mRNA will not adversely affect the subject.

C. Applications and Conditions to be Treated

As indicated above, the present invention concerns inhibition of hair growth, and consequent hair removal, and is applicable to a number of different therapeutic, cosmetic, and industrial applications. The methods can be readily adapted to any of the various mammals having hairless protein analogs, for example, human, mouse, rat, cattle (and other bovines), equines.

1. Long Term (Permanent) Hair Removal

Permanent, or at least long term, hair removal can involve inhibition of hairless protein. Such hair removal is useful for both cosmetic and therapeutic applications. Exemplary cosmetic applications can include, for example, back and chest hair for men and upper lip, eyebrow, leg, arm, underarm, and pubic hair for women.

In addition to cosmetic applications, permanent or long term hair removal is also useful in certain conditions, e.g., trachoma, the various forms of hypertrichosis, and hirsutism.

Hypertrichosis

Hypertrichosis describes all forms of hair growth that are excessive for the bodily location and age of an individual, and which do not result from androgen stimulation. The present invention can be used for the various forms and causes of hypertrichosis, e.g., those described herein.

Hypertrichosis is usually categorized on the basis of the age of onset (at birth or during later years), the extent of distribution (universal or localized), the site of involvement (elbows, anterior or posterior neck), and the cause (genetic or acquired).

Acquired hypertrichosis may result from the use of particular drugs, for example, oral minoxidil, phenyloin, and cyclosporin. Acquired hypertrichosis lanuginosa may also be a manifestation of an underlying malignancy. In the dermatological literature, this is known as “malignant down”. Additional causes of acquired hypertrichosis include hormonal imbalances, malnutrition, HIV and local inflammation.

In addition, some forms of hypertrichosis are clearly hereditary but the genes involved generally remain unknown. Genetic forms of hypertrichosis are very rare human disorders.

There are only a small number of human disorders that have generalized congenital hypertrichosis as the leading phenotypic feature. These include:

Hypertrichosis universalis (MIM145700)

Hypertrichosis universalis congenita, Ambras type (MIM145701)

Gingival fibromatosis with hypertrichosis (MIMI 35400)

Barber-Say syndrome (MIM209885)

Amaurosis congenita, cone-rod type, with hypertrichosis (MIM204110),

CAHMR syndrome (MIM21770)

Cantu syndrome (MIM239850)

Gingival fibromatosis with hypertrichosis and mental retardation MIM605400)

X-linked hypertrichosis (MIM307150)

Acromegaly and hypertrichosis (Irvine et al, 1996).

Of these, only Hypertrichosis universalis, Ambras type hypertrichosis, and X-linked hypertrichosis have excessive hair as the predominant feature. In all the other listed syndromes hypertrichosis is associated with additional more prominent abnormalities. The present invention can be used to treat hypertrichosis, e.g., in any of the conditions listed above, as well as in other conditions in which trichosis occurs.

Trachoma

Trachoma is the leading cause of blindness worldwide. The World Health Organization estimates that there are 146 million people with trachoma and that the disease has caused blindness in 5.9 million people, 15% of the world's blindness. Trachoma is caused by the gram-negative bacterium Chlamydia trachomatis, an intracellular parasite transmitted by fly infestation. In trachoma, the conjunctival lining of the eyelids becomes infected with the bacterium, which over the long term, causes an inflammatory response. The inflammation can lead to scarring, shortening of the lid and in-turning of the eyelashes. Trichiasis, the condition when eyelashes rub on the cornea, can lead to blindness. An estimated 10.6 million adults have inturned eyelashes that require surgery.

While it is advantageous of the Chlamydia infection is prevented, or treated before in-turning of the eyelashes, there is a need for non-surgical approaches to treatment that can at least reduce the corneal scarring. Thus, removal of the eyelash hairs (without leaving stubble) using the present invention can substantially slow, or even prevent such corneal damage, thereby preserving the individual's vision.

Trichiasis

In addition to trachoma, in-turned eyelashes (trichiasis) can have other causes, and are a common source of recurrent ocular irritation for some patients. The in-turned lash (or lashes) in contact with the conjunctiva and/or cornea may lead to a foreign body sensation, localized conjunctival injection, pain and photophobia.

Trichiasis is the term used for misdirection or aberrant placement of eyelashes along the eyelid margin resulting in lash growth toward the cornea. Trichiasis is an acquired condition that may be caused by the following inflammatory or traumatic processes involving the eyelids. The present invention can be used in all cases of trichiasis, including those in the following causal situations:

Chronic blepharitis with meibomianitis—chronic inflammatory changes within the tarsal plate and posterior eyelid margin may cause destruction and misdirection of lash follicles, resulting in chronic trichiasis.

Lid lacerations and thermal burns to the lid margin—may cause redirection of the lash roots with resultant trichiasis.

Previous surgery on eyelids—For example, lid adhesions (tarsorrhaphys) done to prevent exposure in some patients with seventh nerve palsies may cause misdirection of lashes. Similarly, in many reconstructive eyelid procedures, the new eyelid margin may contain fine skin hairs (lanugo-type) that rub on the cornea.

Mucocutaneous diseases—Stevens-Johnson syndrome and Ocular Cicatricial Pemphigoid result not only in the destruction of the eyelid margins and trichiasis but also in the formation of new lashes from the meibomian gland orifices (a condition referred to as distichiasis).

Other cicatricial conjunctival diseases—Herpes Simplex conjunctivitis and Herpes Zoster may cause a cicatrizing conjunctivitis with destruction of the lid margin and lash follicles. Trachoma may also cause a chronic tarsitis with cicatrizing conjunctivitis in the upper or lower eyelid and resultant trichiasis (as well as a cicatricial entropion).

Irradiation and chemical burns—Therapeutic irradiation for eyelid cancers or alkali burns may lead to a disruption of the normal eyelid margin anatomy and resultant misdirection of eyelashes. Both of these processes may also lead to metaplasia of squamous epithelium of the mucocutaneous margin of the eyelid with resultant keratinization, a source of ocular irritation. In addition, destruction of the goblet cells, accessory lacrimal glands, and lacrimal gland will disrupt the normal tear flow, compounding the above problems.

Other conditions in which eyelashes contact the cornea also exist, and the present invention can be used in those cases also. For example:

A condition similar to trichiasis is Eyelid entropion—True entropion (e.g. involutional type seen in the aging population) is characterized by a normal eyelid margin architecture: the eyelid inverts as a result of eyelid laxity, allowing the eyelashes to rub on the cornea. Several of the entities mentioned above (Ocular Pemphigoid, Stevens-Johnson Syndrome) may cause a cicatrization of the conjunctiva as well as the lid margin and create a cicatricial entropion with trichiasis (i.e. the eyelid is inverted due to a cicatricial process). In addition, eyelashes may be misdirected not only due to the lid position, but also due to the inflammatory process involving the actual lash follicles. Therefore, sometimes there may be two problems present (entropion and trichiasis) both of which may require treatment.

Epiblepharon—Epiblepharon is a congenital condition commonly seen in the lower Asian eyelid. A fold of skin and muscle roll upwards and presses the lashes toward the cornea. This does not represent true trichiasis.

Distichiasis—is an abnormality in which an aberrant second row of lashes, (usually from the meibomian gland orifices) grows behind the normal lash line. It may be congenital or acquired. Any process causing chronic inflammation of the lid margin and meibomian glands may transform the meibomian glands into pilosebaceous units capable of producing hair (e.g. chronic blepharitis).

Combined eyelid margin process—Several of the eyelid processes mentioned (Stevens-Johnson syndrome, Ocular Pemphigoid, irradiation, chemical burns) not only may cause entropion and trichiasis, but in addition may lead to squamous metaplasia and keratinization of the non-keratinizing squamous epithelium of the eyelid margin. Keratinized tissue is very irritating to the eye. Therefore, several factors may contribute to the ocular irritation, and as a result, several types of treatment could be required.

Marginal entropion—Is a subtle form of entropion that is seen only at the lid margin. Usually there is chronic inflammation at the eyelid margin with a mild cicatricial process that is starting to roll the lid margin inward. The eyelashes appear more vertical with some truly trichiatic lashes. The clinical clue is the meibomian gland orifices. Normally they should be vertical and not covered by conjunctival epithelium. If the openings are rolled inward and conjunctiva is growing over the opening, then marginal entropion is present in addition to trichiasis. It is important to distinguish this condition when considering treatment.

Hirsutism

Hirsutism is excessive hair growth on a female in a male growth pattern, typically excessive facial hair. Hirsutism is usually caused by an increased sensitivity of the skin to a group of hormones called androgens (testosterone and androstenedione) or increased production of these hormones. Androgen disorders (hyperandrogenism) affects between 5% to 10% of all women. Hair from this condition can be removed in full or part using the present invention.

Pseudofolliculitis barbae

Pseudofolliculitis barbae (razor bumps) is a common condition of the beard area occurring in African American men and other people with curly hair. The problem results when highly curved hairs grow back into the skin causing inflammation and a foreign body reaction. Over time, this can cause keloidal scarring which looks like hard bumps of the beard area and neck. Currently this is usually addressed by attempting to prevent the hair from curving back and growing into the skin with altered shaving practices and the like. The present invention can be used to eliminate hairs causing such difficulties.

Experimental Animals

Permanent hair removal as described herein can also be used with experimental animals to remove hair from all or a portion of the body of an experimental animal. Thus, for example, a hairless spot can be created on a mouse, rat, sheep, monkey, chimpanzee, rabbit or other animal for application over an extended period of time of topically applied pharmaceutical compounds or other materials. Thus, the present invention can be used for this purpose, either with or without shaving shaveing, waxing, or depilation, or other such treatment. In some cases, the hairless spot or area on the animal is initially created with shaving, waxing, or other hair removal method, and the present invention allows the bare area to be maintained (which may be after a sustained period of application of the present compositions, e.g., at least 2, 4, 7, or 10 days, or 2, 3, 4, 5, 6, 8, 10, 12, weeks or even longer).

Industrial Applications

In addition, permanent hair removal as described herein can also be useful to remove hair from mammals whose hides will be used for leather. Dehairing is one of the main initial steps in leather production. Five methods of dehairing are commonly used: i.e., (i) clipping process, (ii) scalding process, (iii) chemical process, (iv) sweating process, and (v) enzymatic process. Of these, the most commonly practiced method of dehairing of hides and skins is the chemical process using lime and sodium sulphide. However, the use of high concentrations of lime and sodium sulphide creates an extremely alkaline environment resulting in the pulping of hair and its subsequent removal, and presents substantial pollution problems. Thus, removal of hairs using the present invention allows hides to be prepared for leather production while eliminating or at least reducing the use of the pollution-causing methods.

D. Use of RNAi and Oligo Sequences

The use of RNAi to reduce or eliminate translation from a targeted mRNA has been described in a number of patents and published patent applications, e.g., as mentioned in the Background of the Invention. In the present invention, particular target sites in hairless protein mRNA can be identified experimentally and/or using software programs to identify accessible sites. For example, procedures such as those described below can be used to identify sites, and to select an optimal site and active oligonucleotide.

Identification of Potential RNAi (e.g., siRNA) Target Sites in any RNA Sequence

The sequence of an RNA target of interest, such as a viral or human mRNA transcript, is screened for target sites, for example by using a computer folding algorithm. In a non-limiting example, the sequence of a gene or RNA gene transcript derived from a database, such as Genbank, is used to generate siNA targets having complementarity to the target. Such sequences can be obtained from a database, or can be determined experimentally as known in the art. Target sites that are known, for example, those target sites determined to be effective target sites based on studies with other nucleic acid molecules, for example ribozymes or antisense, or those targets known to be associated with a disease or condition such as those sites containing mutations or deletions, can be used to design siNA molecules targeting those sites as well. Various parameters can be used to determine which sites are the most suitable target sites within the target RNA sequence. These parameters include but are not limited to secondary or tertiary RNA structure, the nucleotide base composition of the target sequence, the degree of homology between various regions of the target sequence, or the relative position of the target sequence within the RNA transcript. Based on these determinations, any number of target sites within the RNA transcript can be chosen to screen siNA molecules for efficacy, for example by using in vitro RNA cleavage assays, cell culture, or animal models. In a non-limiting example, anywhere from 1 to 1000 target sites are chosen within the transcript based on the size of the siNA construct to be used. High throughput screening assays can be developed for screening siNA molecules using methods known in the art, such as with multi-well or multi-plate assays or combinatorial/siNA library screening assays to determine efficient reduction in target gene expression.

Selection of siNA Molecule Target Sites in a RNA

The following non-limiting steps can be used to carry out the selection of siNAs targeting a given gene sequence or transcript.

• • 1 The target sequence is parsed in silico into a list of all fragments or subsequences of a particular length, for example 23 nucleotide fragments, contained within the target sequence. This step is typically carried out using a custom Perl script, but commercial sequence analysis programs such as Oligo, MacVector, or the GCG Wisconsin Package can be employed as well.
  • 2 In some instances the siNAs correspond to more than one target sequence; such would be the case for example in targeting different transcripts of the same gene, targeting different transcripts of more than one gene, or for targeting both the human gene and an animal homolog. In this case, a subsequence list of a particular length is generated for each of the targets, and then the lists are compared to find matching sequences in each list. The subsequences are then ranked according to the number of target sequences that contain the given subsequence; the goal is to find subsequences that are present in most or all of the target sequences. Alternately, the ranking can identify subsequences that are unique to a target sequence, such as a mutant target sequence. Such an approach would enable the use of siNA to target specifically the mutant sequence and not effect the expression of the normal sequence.
  • 3 In some instances the siNA subsequences are absent in one or more sequences while present in the desired target sequence; such would be the case if the siNA targets a gene with a paralogous family member that is to remain untargeted. As in case 2 above, a subsequence list of a particular length is generated for each of the targets, and then the lists are compared to find sequences that are present in the target gene but are absent in the untargeted paralog.
  • 4 The ranked siNA subsequences can be further analyzed and ranked according to GC content. A preference can be given to sites containing 30-70% GC, with a further preference to sites containing 40-60% GC.
  • 5 The ranked siNA subsequences can be further analyzed and ranked according to self-folding and internal hairpins. Weaker internal folds are preferred; strong hairpin structures are to be avoided.
  • 6 The ranked siNA subsequences can be further analyzed and ranked according to whether they have runs of GGG or CCC in the sequence. GGG (or even more Gs) in either strand can make oligonucleotide synthesis problematic and can potentially interfere with RNAi activity, so it is avoided whenever better sequences are available. CCC is searched in the target strand because that will place GGG in the antisense strand.
  • 7 The ranked siNA subsequences can be further analyzed and ranked according to whether they have the dinucleotide UU (uridine dinucleotide) on the 3′-end of the sequence, and/or AA on the 5′-end of the sequence (to yield 3′ UU on the antisense sequence). These sequences allow one to design siNA molecules with terminal TT thymidine dinucleotides.
  • 8 Four or five target sites are chosen from the ranked list of subsequences as described above. For example, in subsequences having 23 nucleotides, the right 21 nucleotides of each chosen 23-mer subsequence are then designed and synthesized for the upper (sense) strand of the siNA duplex, while the reverse complement of the left 21 nucleotides of each chosen 23-mer subsequence are then designed and synthesized for the lower (antisense) strand of the siNA duplex. If terminal TT residues are desired for the sequence (as described in paragraph 7), then the two 3′ terminal nucleotides of both the sense and antisense strands are replaced by TT prior to synthesizing the oligos.
  • 9 The siNA molecules are screened in an in vitro, cell culture or animal model system to identify the most active siNA molecule or the most preferred target site within the target RNA sequence.

In an alternate approach, a pool of siNA constructs specific to a target sequence is used to screen for target sites in cells expressing target RNA, such as human lung HeLa cells. A non-limiting example of such as pool is a pool comprising sequences having antisense sequences complementary to the target RNA sequence and sense sequences complementary to the antisense sequences. Cells (e.g., HeLa cells) expressing the target gene are transfected with the pool of siNA constructs and cells that demonstrate a phenotype associated with gene silencing are sorted. The pool of siNA constructs can be chemically modified as described herein and synthesized, for example, in a high throughput manner. The siNA from cells demonstrating a positive phenotypic change (e.g., decreased target mRNA levels or target protein expression), are identified, for example by positional analysis within the assay, and are used to determine the most suitable target site(s) within the target RNA sequence based upon the complementary sequence to the corresponding siNA antisense strand identified in the assay.

Exemplary siNA Design

siNA target sites are chosen by analyzing sequences of the target RNA target and optionally prioritizing the target sites on the basis of folding (structure of any given sequence analyzed to determine siNA accessibility to the target), by using a library of siNA molecules as described, or alternately by using an in vitro siNA system as described herein. siNA molecules were designed that could bind each target and are optionally individually analyzed by computer folding to assess whether the siNA molecule can interact with the target sequence. Varying the length of the siNA molecules can be chosen to optimize activity. Generally, a sufficient number of complementary nucleotide bases are chosen to bind to, or otherwise interact with, the target RNA, but the degree of complementarity can be modulated to accommodate siNA duplexes or varying length or base composition. By using such methodologies, siNA molecules can be designed to target sites within any known RNA sequence, for example those RNA sequences corresponding to the any gene transcript.

Chemically modified siNA constructs are designed to provide nuclease stability for systemic administration in vivo and/or improved pharmacokinetic, localization, and delivery properties while preserving the ability to mediate RNAi activity. Chemical modifications as described herein are introduced synthetically using synthetic methods described herein and those generally known in the art. The synthetic siNA constructs are then assayed for nuclease stability in serum and/or cellular/tissue extracts (e.g. liver extracts). The synthetic siNA constructs are also tested in parallel for RNAi activity using an appropriate assay, such as a luciferase reporter assay as described herein or another suitable assay that can quantity RNAi activity. Synthetic siNA constructs that possess both nuclease stability and RNAi activity can be further modified and re-evaluated in stability and activity assays. The chemical modifications of the stabilized active siNA constructs can then be applied to any siNA sequence targeting any chosen RNA and used, for example, in target screening assays to pick lead siNA compounds for therapeutic development.

RNAi In Vitro Assay to Assess siNA Activity

An in vitro assay that recapitulates RNAi in a cell free system is used to evaluate siNA constructs specific to target RNA. The assay comprises the system described by Tuschl et al., 1999, Genes and Development, 13, 3191-3197 and Zamore et al., 2000, Cell, 101, 25-33 adapted for use with a specific target RNA. A Drosophila extract derived from syncytial blastoderm is used to reconstitute RNAi activity in vitro. Target RNA is generated via in vitro transcription from an appropriate plasmid using T7 RNA polymerase or via chemical synthesis as described herein. Sense and antisense siNA strands (for example 20 uM each) are annealed by incubation in buffer (such as 100 mM potassium acetate, 30 mM HEPES-KOH, pH 7.4, 2 mM magnesium acetate) for 1 min. at 90° C. followed by 1 hour at 37° C., then diluted in lysis buffer (for example 100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate). Annealing can be monitored by gel electrophoresis on an agarose gel in TBE buffer and stained with ethidium bromide. The Drosophila lysate is prepared using zero to two hour old embryos from Oregon R flies collected on yeasted molasses agar that are dechorionated and lysed. The lysate is centrifuged and the supernatant isolated. The assay comprises a reaction mixture containing 50% lysate [vol/vol], RNA (10-50 pM final concentration), and 10% [vol/vol] lysis buffer containing siNA (10 nM final concentration). The reaction mixture also contains 10 mM creatine phosphate, 10 ug.ml creatine phosphokinase, 100 um GTP, 100 uM UTP, 100 uM CTP, 500 uM ATP, 5 mM DTT, 0.1 U/uL RNasin (Promega), and 100 uM of each amino acid. The final concentration of potassium acetate is adjusted to 100 mM. The reactions are pre-assembled on ice and preincubated at 25° C. for 10 minutes before adding RNA, then incubated at 25° C. for an additional 60 minutes. Reactions are quenched with 4 volumes of 1.25× Passive Lysis Buffer (Promega). Target RNA cleavage is assayed by RT-PCR analysis or other methods known in the art and are compared to control reactions in which siNA is omitted from the reaction.

Alternately, internally-labeled target RNA for the assay is prepared by in vitro transcription in the presence of [a-³²P] CTP, passed over a G 50 Sephadex column by spin chromatography and used as target RNA without further purification. Optionally, target RNA is 5′-³²P-end labeled using T4 oligonucleotide kinase enzyme. Assays are performed as described above and target RNA and the specific RNA cleavage products generated by RNAi are visualized on an autoradiograph of a gel. The percentage of cleavage is determined by Phosphor Imager® quantitation of bands representing intact control RNA or RNA from control reactions without siNA and the cleavage products generated by the assay.

In one embodiment, this assay is used to determine target sites in the RNA target for siNA mediated RNAi cleavage, wherein a plurality of siNA constructs are screened for RNAi mediated cleavage of the RNA target, for example by analyzing the assay reaction by electrophoresis of labeled target RNA, or by northern blotting, as well as by other methodology well known in the art.

Specific hairless protein target sequences and the complementary sequences are provided as 19-mers in Table 1 following the Examples. In the table, the oligo number (first column on the left), e.g., 1, 2, 3, etc. matches the 1^st (5′) nucleotide in the reference sense cDNA sequence. Thus, Oligonucleotide 1 begins at nucleotide 1 in the reference hairless cDNA sequence, Oligonucleotide 2, begins at nucleotide 2 in the reference sequence, and so on. Thus, one skilled in the art recognizes that the nucleotide position of each nucleotide in each oligonucleotide in Table 1 is specified as if each nucleotide were marked with the respective number.

The sequences shown in Table 1 are provided as DNA sequences, but one skilled in the art understands that Table 1 also describes the matching RNA sequence. One skilled in the art understands that the RNA sequence has a U replacing each T shown in the DNA sequence. For example, for Oligonucleotide 1 in Table 1, the DNA sequence is 5′-TCTCCCGGGAGCCACTCCC-3′ (SEQ ID NO: 1), and the matching RNA sequence is 5′-UCUCCCGGGAGCCACUCCC-3′ (SEQ ID NO: 11332).

While oligonucleotides are shown in Table 1 as 19-mers, this description expressly includes the additional 20-mer, 21-mer, 22-mer, 23-mer, 24-mer, 25-mer, 26-mer, 27-mer, 28-mer, and 29-mer oligonucleotides as if they were included in the table. The sequence descriptions of those 20-29-mers is provided by taking a starting 19-mer that has the same 5′-nucleotide as the respective 20-29-mer, and adding the next 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 3′-nucleotides from the subsequent 19-mer oligonucleotides from the table. Thus, for example, the 19-mer sense RNA Oligonucleotide 4 has the sequence:

5′-CCCGGGAGCCACUCCCAUG-3′ (SEQ ID NO: 11333)

and the complementary 19-mer RNA described has the sequence

5′-CAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO: 11334)

Further, a 20-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next nucleotide 3′, i.e., the 3′-terminal G from Oligo 5. Thus, the 20-mer RNA described has the sequence

5′-CCCGGGAGCCACUCCCAUGG-3′ (SEQ ID NO: 11335)

and the complementary 20-mer RNA described has the sequence

5′-CCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO: 11336)

Similarly, a 21-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next two nucleotides 3′, i.e., the 3′-terminal GG from Oligo 6. Thus, the 21-mer RNA described has the sequence

5′-CCCGGGAGCCACUCCCAUGGG-3′ (SEQ ID NO: 11337)

and the complementary 21-mer RNA described has the sequence

5′-CCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO: 11338)

As the next oligonucleotide described, a 22-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next three nucleotides 3′, i.e., the 3′-terminal GGC from Oligo 7. Thus, the 22-mer RNA described has the sequence

5′-CCCGGGAGCCACUCCCAUGGGC-3′ ((SEQ ID NO: 11339)

and the complementary 22-mer RNA described has the sequence

5′-GCCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO: 11340)

A 23-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next four nucleotides 3′, i.e., the 3′-terminal GGCG from Oligo 8. Thus, the 23-mer RNA described has the sequence

5′-CCCGGGAGCCACUCCCAUGGGCG-3′ (SEQ ID NO: 11341)

and the complementary 23-mer RNA described has the sequence

5′-CGCCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO: 11342)

A 24-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next five nucleotides 3′, i.e., the 3′-terminal GGCGC from Oligo 9. Thus, the 24-mer RNA described has the sequence

5′-CCCGGGAGCCACUCCCAUGGGCGC-3′ (SEQ ID NO: 11343)

and the complementary 24-mer RNA described has the sequence

5′-GCGCCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO: 11344)

In similar fashion, a 25-mer that includes the Oligonucleotide 4 sequence is described as

5′-CCCGGGAGCCACUCCCAUGGGCGCC-3′ (SEQ ID NO: 11345)

and the complementary 25-mer RNA described has the sequence

5′-GGCGCCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO: 11346)

A 26-mer that includes the Oligonucleotide 4 sequence is described as

5′-CCCGGGAGCCACUCCCAUGGGCGCCU-3′ (SEQ ID NO: 11347)

and the complementary 26-mer RNA described has the sequence

(SEQ ID NO: 11348)
5′-AGGCGCCCAUGGGAGUGGCUCCCGGG-3′.

A 27-mer that includes the Oligonucleotide 4 sequence is described as

(SEQ ID NO: 11349)
5′-CCCGGGAGCCACUCCCAUGGGCGCCUC-3′

and the complementary 27-mer RNA described has the sequence

(SEQ ID NO: 11350)
5′-GAGGCGCCCAUGGGAGUGGCUCCCGGG-3′.

A 28-mer that includes the Oligonucleotide 4 sequence is described as

(SEQ ID NO: 11351)
5′-CCCGGGAGCCACUCCCAUGGGCGCCUCU-3′

and the complementary 28-mer RNA described has the sequence

(SEQ ID NO: 11352)
5′-AGAGGCGCCCAUGGGAGUGGCUCCCGGG-3′.

A 29-mer that includes the Oligonucleotide 4 sequence is described as

(SEQ ID NO: 11353)
5′-CCCGGGAGCCACUCCCAUGGGCGCCUCUC-3′

and the complementary 29-mer RNA described has the sequence

(SEQ ID NO: 11354)
5′-GAGAGGCGCCCAUGGGAGUGGCUCCCGGG-3′.

Thus, Table 1 describes each of the 19-mers shown in Table 1 as DNA and RNA, and the corresponding 20-mers and longer.

In addition, the Table describes double stranded oligonucleotides with the sense and antisense oligonucleotide strands hybridized, as well as such double stranded oligonucleotides with one or both strands having a 3′-overhang. Such an overhang consists of one or more 3′-terminal nucleotides of an oligonucleotide strand in a double stranded molecule that are not hybridized with the complementary strand. In the present case, such overhang nucleotides often match the corresponding nucleotides from the target mRNA sequence, but can be different.

Table 1 also describes oligonucleotides that contain known polymorphisms. Those polymorphic sites are described in Table 2 along with the replacement nucleotide. Thus, Table 1 with Table 2 describes the oligonucleotides with the alternate nucleotides at a polymorphic site.

Chemical Modifications

As indicated above, for many applications it is advantageous to use chemically modified oligonucleotides rather than unmodified RNA for RNAi (e.g., siRNA). Such modification can dramatically increase the cellular and/or serum lifetime of the modified oligonucleotide compared to the unmodified form.

Description of such chemical modification is provided in McSwiggen et al., PCT/US03/05346, WO 03/070918. Thus, the introduction of chemically modified nucleotides into nucleic acid molecules assists in overcoming potential limitations of in vivo stability and bioavailability inherent to native RNA molecules that are delivered exogenously. For example, the use of chemically modified nucleic acid molecules can enable a lower dose of a particular nucleic acid molecule for a given therapeutic effect since chemically modified nucleic acid molecules tend to have a longer half-life in serum. Furthermore, certain chemical modifications can improve the bioavailability of nucleic acid molecules by targeting particular cells or tissues and/or improving cellular uptake of the nucleic acid molecule. Therefore, even if the activity of a chemically modified nucleic acid molecule is reduced as compared to a native nucleic acid molecule, for example when compared to an all RNA nucleic acid molecule, the overall activity of the modified nucleic acid molecule can be greater than the native molecule due to improved stability and/or delivery of the molecule. Unlike native unmodified siRNA, chemically modified siNA can also minimize the possibility of activating interferon activity in humans.

Thus, in some embodiments of the present invention, the nucleic acid molecules that act as mediators of the RNA interference gene silencing response are chemically modified double stranded nucleic acid molecules, generally about 19-29 nucleotides in length. The most active siRNA molecules are thought to have such duplexes with overhanging ends of 1-3 nucleotides, for example 21 nucleotide duplexes with 19 base pairs and 2 nucleotide 3′-overhangs. These overhanging segments are readily hydrolyzed by endonucleases in vivo. Studies have shown that replacing the 3′-overhanging segments of a 21-mer siRNA duplex having 2 nucleotide 3′ overhangs with deoxyribonucleotides does not have an adverse effect on RNAi activity. Replacing up to 4 nucleotides on each end of the siRNA with deoxyribonucleotides has been reported to be well tolerated whereas complete substitution with deoxyribonucleotides results in no RNAi activity (Elbashir et al., 2001, EMBO J., 20, 6877). In addition, Elbashir et al. also report that full substitution of siRNA with 2′-O-methyl nucleotides completely abolishes RNAi activity.

In some embodiments, the chemically modified siNA constructs having specificity for target nucleic acid molecules in a cell. Non-limiting examples of such chemical modifications include without limitation phosphorothioate internucleotide linkages, 2′-O-methyl ribonucleotides, 2′-deoxy-2′-fluoro ribonucleotides, “universal base” nucleotides, 5-C-methyl nucleotides, and inverted deoxyabasic residue incorporation. These chemical modifications, when used in various siNA constructs, are shown to preserve RNAi activity in cells while at the same time, dramatically increasing the serum stability of these compounds. Furthermore, contrary to the data published by Parrish et al., supra, applicant demonstrates that multiple (greater than one) phosphorothioate substitutions are well-tolerated and confer substantial increases in serum stability for modified siNA constructs.

In one embodiment, a siNA molecule of the invention comprises modified nucleotides while maintaining the ability to mediate RNAi. The modified nucleotides can be used to improve in vitro or in vivo characteristics such as stability, activity, and/or bioavailability. For example, a siNA molecule of the invention can comprise modified nucleotides as a percentage of the total number of nucleotides present in the siNA molecule. As such, a siNA molecule of the invention can generally comprise modified nucleotides at between 5 and 100% of the nucleotide positions (e.g., 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotide positions). The actual percentage of modified nucleotides present in a given siNA molecule will depend on the total number of nucleotides present in the siNA. If the siNA molecule is single stranded, the percent modification can be based upon the total number of nucleotides present in the single stranded siNA molecules. Likewise, if the siNA molecule is double stranded, the percent modification can be based upon the total number of nucleotides present in the sense strand, antisense strand, or both the sense and antisense strands. In addition, the actual percentage of modified nucleotides present in a given siNA molecule can also depend on the total number of purine and pyrimidine nucleotides present in the siNA, for example wherein all pyrimidine nucleotides and/or all purine nucleotides present in the siNA molecule are modified.

In a non-limiting example, the introduction of chemically-modified nucleotides into nucleic acid molecules will provide a powerful tool in overcoming potential limitations of in vivo stability and bioavailability inherent to native RNA molecules that are delivered exogenously. For example, the use of chemically-modified nucleic acid molecules can enable a lower dose of a particular nucleic acid molecule for a given therapeutic effect since chemically-modified nucleic acid molecules tend to have a longer half-life in serum. Furthermore, certain chemical modifications can improve the bioavailability of nucleic acid molecules by targeting particular cells or tissues and/or improving cellular uptake of the nucleic acid molecule. Therefore, even if the activity of a chemically-modified nucleic acid molecule is reduced as compared to a native nucleic acid molecule, for example when compared to an all-RNA nucleic acid molecule, the overall activity of the modified nucleic acid molecule can be greater than that of the native molecule due to improved stability and/or delivery of the molecule. Unlike native unmodified siNA, chemically-modified siNA can also minimize the possibility of activating interferon activity in humans.

The antisense region of a siNA molecule of the invention can comprise a phosphorothioate internucleotide linkage at the 3′-end of said antisense region. The antisense region can comprise between about one and about five phosphorothioate internucleotide linkages at the 5′-end of said antisense region. The 3′-terminal nucleotide overhangs of a siNA molecule of the invention can comprise ribonucleotides or deoxyribonucleotides that are chemically-modified at a nucleic acid sugar, base, or backbone. The 3′-terminal nucleotide overhangs can comprise one or more universal base ribonucleotides. The 3′-terminal nucleotide overhangs can comprise one or more acyclic nucleotides.

In certain embodiments, the chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, includes one or more chemically modified nucleotides (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) comprising a backbone modified internucleotide linkage having Formula I:

##STR00001##
wherein each R1 and R2 is independently any nucleotide, non-nucleotide, or oligonucleotide which can be naturally-occurring or chemically-modified, each X and Y is independently O, S, N, alkyl, or substituted alkyl, each Z and W is independently O, S, N, alkyl, substituted alkyl, O-alkyl, S-alkyl, alkaryl, or aralkyl, and wherein W, X, Y, and Z are optionally not all O.

The chemically-modified internucleotide linkages having Formula I, for example wherein any Z, W, X, and/or Y independently comprises a sulphur atom, can be present in one or both oligonucleotide strands of the siNA duplex, for example in the sense strand, the antisense strand, or both strands. The siNA molecules of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) chemically-modified internucleotide linkages having Formula I at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense strand, the antisense strand, or both strands. For example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified internucleotide linkages having Formula I at the 5′-end of the sense strand, the antisense strand, or both strands. In another non-limiting example, an exemplary siNA molecule of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) pyrimidine nucleotides with chemically-modified internucleotide linkages having Formula I in the sense strand, the antisense strand, or both strands. In yet another non-limiting example, an exemplary siNA molecule of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) purine nucleotides with chemically-modified internucleotide linkages having Formula I in the sense strand, the antisense strand, or both strands. In another embodiment, a siNA molecule of the invention having internucleotide linkage(s) of Formula I also comprises a chemically-modified nucleotide or non-nucleotide having any of Formulae I-VII.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) nucleotides or non-nucleotides having Formula II:

##STR00002##
wherein each R3, R4, R5, R6, R7, R8, R10, R1 and R12 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or group having Formula I; R9 is O, S, CH2, S═O, CHF, or CF2, and B is a nucleosidic base such as adenine, guanine, uracil, cytosine, thymine, 2-aminoadenosine, 5-methylcytosine, 2,6-diaminopurine, or any other non-naturally occurring base that can be complementary or non-complementary to target RNA or a non-nucleosidic base such as phenyl, naphthyl, 3-nitropyrrole, 5-nitroindole, nebularine, pyridone, pyridinone, or any other non-naturally occurring universal base that can be complementary or non-complementary to target RNA.

The chemically-modified nucleotide or non-nucleotide of Formula II can be present in one or both oligonucleotide strands of the siNA duplex, for example in the sense strand, the antisense strand, or both strands. The siNA molecules of the invention can comprise one or more chemically-modified nucleotide or non-nucleotide of Formula II at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense strand, the antisense strand, or both strands. For example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified nucleotides or non-nucleotides of Formula II at the 5′-end of the sense strand, the antisense strand, or both strands. In anther non-limiting example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified nucleotides or non-nucleotides of Formula II at the 3′-end of the sense strand, the antisense strand, or both strands.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) nucleotides or non-nucleotides having Formula III:

##STR00003##
wherein each R3, R4, R5, R6, R7, R8, R10, R11 and R12 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or group having Formula I; R9 is O, S, CH2, S═O, CHF, or CF2, and B is a nucleosidic base such as adenine, guanine, uracil, cytosine, thymine, 2-aminoadenosine, 5-methylcytosine, 2,6-diaminopurine, or any other non-naturally occurring base that can be employed to be complementary or non-complementary to target RNA or a non-nucleosidic base such as phenyl, naphthyl, 3-nitropyrrole, 5-nitroindole, nebularine, pyridone, pyridinone, or any other non-naturally occurring universal base that can be complementary or non-complementary to target RNA.

The chemically-modified nucleotide or non-nucleotide of Formula III can be present in one or both oligonucleotide strands of the siNA duplex, for example in the sense strand, the antisense strand, or both strands. The siNA molecules of the invention can comprise one or more chemically-modified nucleotide or non-nucleotide of Formula III at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense strand, the antisense strand, or both strands. For example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified nucleotide(s) or non-nucleotide(s) of Formula III at the 5′-end of the sense strand, the antisense strand, or both strands. In anther non-limiting example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified nucleotide or non-nucleotide of Formula III at the 3′-end of the sense strand, the antisense strand, or both strands.

In another embodiment, a siNA molecule of the invention comprises a nucleotide having Formula II or III, wherein the nucleotide having Formula II or III is in an inverted configuration. For example, the nucleotide having Formula II or III is connected to the siNA construct in a 3′-3′,3′-2′,2′-3′, or 5′-5′ configuration, such as at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of one or both siNA strands.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises a 5′-terminal phosphate group having Formula IV:

##STR00004##
wherein each X and Y is independently O, S, N, alkyl, substituted alkyl, or alkylhalo; wherein each Z and W is independently O, S, N, alkyl, substituted alkyl, O-alkyl, S-alkyl, alkaryl, aralkyl, or alkylhalo; and wherein W, X, Y and Z are not all O.

In one embodiment, the invention features a siNA molecule having a 5′-terminal phosphate group having Formula IV on the target-complementary strand, for example a strand complementary to a target RNA, wherein the siNA molecule comprises an all RNA siNA molecule. In another embodiment, the invention features a siNA molecule having a 5′-terminal phosphate group having Formula IV on the target-complementary strand wherein the siNA molecule also comprises about 1-3 (e.g., about 1, 2, or 3) nucleotide 3′-terminal nucleotide overhangs having between about 1 and about 4 (e.g., about 1, 2, 3, or 4) deoxyribonucleotides on the 3′-end of one or both strands. In another embodiment, a 5′-terminal phosphate group having Formula IV is present on the target-complementary strand of a siNA molecule of the invention, for example a siNA molecule having chemical modifications having any of Formulae I-VII.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises one or more phosphorothioate internucleotide linkages. For example, in a non-limiting example, the invention features a chemically-modified short interfering nucleic acid (siNA) having about 1, 2, 3, 4, 5, 6, 7, 8 or more phosphorothioate internucleotide linkages in one siNA strand. In yet another embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) individually having about 1, 2, 3, 4, 5, 6, 7, 8 or more phosphorothioate internucleotide linkages in both siNA strands. The phosphorothioate internucleotide linkages can be present in one or both oligonucleotide strands of the siNA duplex, for example in the sense strand, the antisense strand, or both strands. The siNA molecules of the invention can comprise one or more phosphorothioate internucleotide linkages at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand, the antisense strand, or both strands. For example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) consecutive phosphorothioate internucleotide linkages at the 5′-end of the sense strand, the antisense strand, or both strands. In another non-limiting example, an exemplary siNA molecule of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) pyrimidine phosphorothioate internucleotide linkages in the sense strand, the antisense strand, or both strands. In yet another non-limiting example, an exemplary siNA molecule of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) purine phosphorothioate internucleotide linkages in the sense strand, the antisense strand, or both strands.

In one embodiment, the invention features a siNA molecule, wherein the sense strand comprises one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′ end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand; and wherein the antisense strand comprises any of between 1 and 10 or more, specifically about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the antisense strand. In another embodiment, one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, pyrimidine nucleotides of the sense and/or antisense siNA strand are chemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoro nucleotides, with or without one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, phosphorothioate internucleotide linkages and/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends, being present in the same or different strand.

In another embodiment, the invention features a siNA molecule, wherein the sense strand comprises between about 1 and about 5, specifically about 1, 2, 3, 4, or 5 phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3-end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand; and wherein the antisense strand comprises any of between about 1 and about 5 or more, specifically about 1, 2, 3, 4, 5, or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the antisense strand. In another embodiment, one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, pyrimidine nucleotides of the sense and/or antisense siNA strand are chemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoro nucleotides, with or without between about 1 and about 5 or more, for example about 1, 2, 3, 4, 5, or more phosphorothioate internucleotide linkages and/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends, being present in the same or different strand.

In one embodiment, the invention features a siNA molecule, wherein the antisense strand comprises one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more phosphorothioate internucleotide linkages, and/or between one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand; and wherein the antisense strand comprises any of between about 1 and about 10, specifically about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the antisense strand. In another embodiment, one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more pyrimidine nucleotides of the sense and/or antisense siNA strand are chemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoro nucleotides, with or without one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more phosphorothioate internucleotide linkages and/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends, being present in the same or different strand.

In another embodiment, the invention features a siNA molecule, wherein the antisense strand comprises between about 1 and about 5 or more, specifically about 1, 2, 3, 4, 5 or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand; and wherein the antisense strand comprises any of between about 1 and about 5 or more, specifically about 1, 2, 3, 4, 5 or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the antisense strand. In another embodiment, one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more pyrimidine nucleotides of the sense and/or antisense siNA strand are chemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoro nucleotides, with or without between about 1 and about 5, for example about 1, 2, 3, 4, 5 or more phosphorothioate internucleotide linkages and/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends, being present in the same or different strand.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule having between about 1 and about 5, specifically about 1, 2, 3, 4, 5 or more phosphorothioate internucleotide linkages in each strand of the siNA molecule.

In another embodiment, the invention features a siNA molecule comprising 2′-5′ internucleotide linkages. The 2′-5′ internucleotide linkage(s) can be at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of one or both siNA sequence strands. In addition, the 2′-5′ internucleotide linkage(s) can be present at various other positions within one or both siNA sequence strands, for example, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more including every internucleotide linkage of a pyrimidine nucleotide in one or both strands of the siNA molecule can comprise a 2′-5′ internucleotide linkage, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more including every internucleotide linkage of a purine nucleotide in one or both strands of the siNA molecule can comprise a 2′-5′ internucleotide linkage.

In another embodiment, a chemically-modified siNA molecule of the invention comprises a duplex having two strands, one or both of which can be chemically-modified, wherein each strand is between about 18 and about 27 (e.g., about 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27) nucleotides in length, wherein the duplex has between about 18 and about 23 (e.g., about 18, 19, 20, 21, 22, or 23) base pairs, and wherein the chemical modification comprises a structure having any of Formulae I-VII. For example, an exemplary chemically-modified siNA molecule of the invention comprises a duplex having two strands, one or both of which can be chemically-modified with a chemical modification having any of Formulae I-VII or any combination thereof, wherein each strand consists of about 21 nucleotides, each having a 2-nucleotide 3′-terminal nucleotide overhang, and wherein the duplex has about 19 base pairs. In another embodiment, a siNA molecule of the invention comprises a single stranded hairpin structure, wherein the siNA is between about 36 and about 70 (e.g., about 36, 40, 45, 50, 55, 60, 65, or 70) nucleotides in length having between about 18 and about 23 (e.g., about 18, 19, 20, 21, 22, or 23) base pairs, and wherein the siNA can include a chemical modification comprising a structure having any of Formulae I-VII or any combination thereof. For example, an exemplary chemically-modified siNA molecule of the invention comprises a linear oligonucleotide having between about 42 and about 50 (e.g., about 42, 43, 44, 45, 46, 47, 48, 49, or 50) nucleotides that is chemically-modified with a chemical modification having any of Formulae I-VII or any combination thereof, wherein the linear oligonucleotide forms a hairpin structure having about 19 base pairs and a 2-nucleotide 3′-terminal nucleotide overhang. In another embodiment, a linear hairpin siNA molecule of the invention contains a stem loop motif, wherein the loop portion of the siNA molecule is biodegradable. For example, a linear hairpin siNA molecule of the invention is designed such that degradation of the loop portion of the siNA molecule in vivo can generate a double-stranded siNA molecule with 3′-terminal overhangs, such as 3′-terminal nucleotide overhangs comprising about 2 nucleotides.

In another embodiment, a siNA molecule of the invention comprises a circular nucleic acid molecule, wherein the siNA is between about 38 and about 70 (e.g., about 38, 40, 45, 50, 55, 60, 65, or 70) nucleotides in length having between about 18 and about 23 (e.g., about 18, 19, 20, 21, 22, or 23) base pairs, and wherein the siNA can include a chemical modification, which comprises a structure having any of Formulae I-VII or any combination thereof. For example, an exemplary chemically-modified siNA molecule of the invention comprises a circular oligonucleotide having between about 42 and about 50 (e.g., about 42, 43, 44, 45, 46, 47, 48, 49, or 50) nucleotides that is chemically-modified with a chemical modification having any of Formulae I-VII or any combination thereof, wherein the circular oligonucleotide forms a dumbbell shaped structure having about 19 base pairs and 2 loops.

In another embodiment, a circular siNA molecule of the invention contains two loop motifs, wherein one or both loop portions of the siNA molecule is biodegradable. For example, a circular siNA molecule of the invention is designed such that degradation of the loop portions of the siNA molecule in vivo can generate a double-stranded siNA molecule with 3′-terminal overhangs, such as 3′-terminal nucleotide overhangs comprising about 2 nucleotides.

In one embodiment, a siNA molecule of the invention comprises at least one (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) abasic moiety, for example a compound having Formula V:

##STR00005##
wherein each R3, R4, R5, R6, R7, R8, R10, R11, R12, and R13 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or group having Formula I; R9 is O, S, CH2, S═O, CHF, or CF2.

In one embodiment, a siNA molecule of the invention comprises at least one (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) inverted abasic moiety, for example a compound having Formula VI:

##STR00006##
wherein each R3, R4, R5, R6, R7, R8, R10, R11, R12, and R13 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or group having Formula I; R9 is O, S, CH2, S═O, CHF, or CF2, and either R2, R3, R8 or R13 serve as points of attachment to the siNA molecule of the invention.

In another embodiment, a siNA molecule of the invention comprises at least one (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) substituted polyalkyl moieties, for example a compound having Formula VII:

##STR00007##
wherein each n is independently an integer from 1 to 12, each R1, R2 and R3 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or a group having Formula I, and R1, R2 or R3 serves as points of attachment to the siNA molecule of the invention.

In another embodiment, the invention features a compound having Formula VII, wherein R1 and R2 are hydroxyl (OH) groups, n=1, and R3 comprises O and is the point of attachment to the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of one or both strands of a double-stranded siNA molecule of the invention or to a single-stranded siNA molecule of the invention. This modification is referred to herein as “glyceryl”.

In another embodiment, a moiety having any of Formula V, VI or VII of the invention is at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of a siNA molecule of the invention. For example, a moiety having Formula V, VI or VII can be present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense strand, the sense strand, or both antisense and sense strands of the siNA molecule. In addition, a moiety having Formula VII can be present at the 3′-end or the 5′-end of a hairpin siNA molecule as described herein.

In another embodiment, a siNA molecule of the invention comprises an abasic residue having Formula V or VI, wherein the abasic residue having Formula VI or VI is connected to the siNA construct in a 3′-3′,3′-2′,2′-3′, or 5′-5′ configuration, such as at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of one or both siNA strands.

In one embodiment, a siNA molecule of the invention comprises one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) locked nucleic acid (LNA) nucleotides, for example at the 5′-end, the 3′-end, both of the 5′ and 3′-ends, or any combination thereof, of the siNA molecule.

In another embodiment, a siNA molecule of the invention comprises one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) acyclic nucleotides, for example at the 5′-end, the 3′-end, both of the 5′ and 3′-ends, or any combination thereof, of the siNA molecule.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises a sense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where any (e.g., one or more or all) purine nucleotides present in the sense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides).

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises a sense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where any (e.g., one or more or all) purine nucleotides present in the sense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides), wherein any nucleotides comprising a 3′-terminal nucleotide overhang that are present in said sense region are 2′-deoxy nucleotides.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises an antisense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any (e.g., one or more or all) purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides).

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises an antisense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any (e.g., one or more or all) purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides), wherein any nucleotides comprising a 3′-terminal nucleotide overhang that are present in said antisense region are 2′-deoxy nucleotides.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises an antisense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where any (e.g., one or more or all) purine nucleotides present in the antisense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides).

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemically-modified siNA comprises a sense region, where one or more pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where one or more purine nucleotides present in the sense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides), and inverted deoxy abasic modifications that are optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense region, the sense region optionally further comprising a 3′-terminal overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxyribonucleotides; and wherein the chemically-modified short interfering nucleic acid molecule comprises an antisense region, where one or more pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein one or more purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the antisense region optionally further comprising a 3′-terminal nucleotide overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxynucleotides, wherein the overhang nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the siNA comprises a sense region, where one or more pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where one or more purine nucleotides present in the sense region are purine ribonucleotides (e.g., wherein all purine nucleotides are purine ribonucleotides or alternately a plurality of purine nucleotides are purine ribonucleotides), and inverted deoxy abasic modifications that are optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense region, the sense region optionally further comprising a 3′-terminal overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxyribonucleotides; and wherein the siNA comprises an antisense region, where one or more pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the antisense region optionally further comprising a 3′-terminal nucleotide overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxynucleotides, wherein the overhang nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemically-modified siNA comprises a sense region, where one or more pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and for example where one or more purine nucleotides present in the sense region are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides (e.g., wherein all purine nucleotides are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides or alternately a plurality of purine nucleotides are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides), and wherein inverted deoxy abasic modifications are optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense region, the sense region optionally further comprising a 3′-terminal overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxyribonucleotides; and wherein the chemically-modified short interfering nucleic acid molecule comprises an antisense region, where one or more pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein one or more purine nucleotides present in the antisense region are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides (e.g., wherein all purine nucleotides are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides or alternately a plurality of purine nucleotides are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides), and a terminal cap modification, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the antisense region optionally further comprising a 3′-terminal nucleotide overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxynucleotides, wherein the overhang nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages.

In another embodiment, any modified nucleotides present in the siNA molecules of the invention, preferably in the antisense strand of the siNA molecules of the invention, comprise modified nucleotides having properties or characteristics similar to naturally occurring ribonucleotides. For example, the invention features siNA molecules including modified nucleotides having a Northern conformation (e.g., Northern pseudorotation cycle, see for example Saenger, Principles of Nucleic Acid Structure, Springer-Verlag ed., 1984). As such, chemically modified nucleotides present in the siNA molecules of the invention, preferably in the antisense strand of the siNA molecules of the invention, are preferably resistant to nuclease degradation while at the same time maintaining the capacity to mediate RNAi. Non-limiting examples of nucleotides having a northern configuration include locked nucleic acid (LNA) nucleotides (e.g., 2′-O,4′-C-methylene-(D-ribofuranosyl) nucleotides); 2′-methoxyethoxy (MOE) nucleotides; 2′-deoxy-2′-fluoro nucleotides, 2′-deoxy-2′-chloro nucleotides, 2′-azido nucleotides, and 2′-O-methyl nucleotides.

In one embodiment, the invention features a chemically-modified short interfering nucleic acid molecule (siNA) capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises one or more conjugates covalently attached to the chemically-modified siNA molecule. In another embodiment, the conjugate is covalently attached to the chemically-modified siNA molecule via a biodegradable linker. In one embodiment, the conjugate molecule is attached at the 3′-end of either the sense strand, the antisense strand, or both strands of the chemically-modified siNA molecule. In another embodiment, the conjugate molecule is attached at the 5′-end of either the sense strand, the antisense strand, or both strands of the chemically-modified siNA molecule. In yet another embodiment, the conjugate molecule is attached both the 3′-end and 5′-end of either the sense strand, the antisense strand, or both strands of the chemically-modified siNA molecule, or any combination thereof. In one embodiment, a conjugate molecule of the invention comprises a molecule that facilitates delivery of a chemically-modified siNA molecule into a biological system such as a cell. In another embodiment, the conjugate molecule attached to the chemically-modified siNA molecule is a poly ethylene glycol, human serum albumin, or a ligand for a cellular receptor that can mediate cellular uptake. Examples of specific conjugate molecules contemplated by the instant invention that can be attached to chemically-modified siNA molecules are described in Vargeese et al., U.S. Ser. No. 60/311,865, incorporated by reference herein. The type of conjugates used and the extent of conjugation of siNA molecules of the invention can be evaluated for improved pharmacokinetic profiles, bioavailability, and/or stability of siNA constructs while at the same time maintaining the ability of the siNA to mediate RNAi activity. As such, one skilled in the art can screen siNA constructs that are modified with various conjugates to determine whether the siNA conjugate complex possesses improved properties while maintaining the ability to mediate RNAi, for example in animal models as are generally known in the art.

In one embodiment, the invention features a short interfering nucleic acid (siNA) molecule of the invention, wherein the siNA further comprises a nucleotide, non-nucleotide, or mixed nucleotide/non-nucleotide linker that joins the sense region of the siNA to the antisense region of the siNA. In another embodiment, a nucleotide linker of the invention can be a linker of ≧2 nucleotides in length, for example 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides in length. In yet another embodiment, the nucleotide linker can be a nucleic acid aptamer. By “aptamer” or “nucleic acid aptamer” as used herein is meant a nucleic acid molecule that binds specifically to a target molecule wherein the nucleic acid molecule has sequence that is comprises a sequence recognized by the target molecule in its natural setting. Alternately, an aptamer can be a nucleic acid molecule that binds to a target molecule where the target molecule does not naturally bind to a nucleic acid. The target molecule can be any molecule of interest. For example, the aptamer can be used to bind to a ligand-binding domain of a protein, thereby preventing interaction of the naturally occurring ligand with the protein. This is a non-limiting example and those in the art will recognize that other embodiments can be readily generated using techniques generally known in the art, see for example Gold et al., 1995, Annu. Rev. Biochem., 64, 763; Brody and Gold, 2000, J. Biotechnol., 74, 5; Sun, 2000, Curr. Opin. Mol. Ther., 2, 100; Kusser, 2000, J. Biotechnol., 74, 27; Hermann and Patel, 2000, Science, 287, 820; and Jayasena, 1999, Clinical Chemistry, 45, 1628.

In yet another embodiment, a non-nucleotide linker of the invention comprises abasic nucleotide, polyether, polyamine, polyamide, peptide, carbohydrate, lipid, polyhydrocarbon, or other polymeric compounds (e.g. polyethylene glycols such as those having between 2 and 100 ethylene glycol units). Specific examples include those described by Seela and Kaiser, Nucleic Acids Res. 1990, 18:6353 and Nucleic Acids Res. 1987, 15:3113; Cload and Schepartz, J. Am. Chem. Soc. 1991, 113:6324; Richardson and Schepartz, J. Am. Chem. Soc. 1991, 113:5109; Ma et al., Nucleic Acids Res. 1993, 21:2585 and Biochemistry 1993, 32:1751; Durand et al., Nucleic Acids Res. 1990, 18:6353; McCurdy et al., Nucleosides & Nucleotides 1991, 10:287; Jschke et al., Tetrahedron Lett. 1993, 34:301; Ono et al., Biochemistry 1991, 30:9914; Arnold et al., International Publication No. WO 89/02439; Usman et al., International Publication No. WO 95/06731; Dudycz et al., International Publication No. WO 95/11910 and Ferentz and Verdine, J. Am. Chem. Soc. 1991, 113:4000, all hereby incorporated by reference herein. A “non-nucleotide” further means any group or compound that can be incorporated into a nucleic acid chain in the place of one or more nucleotide units, including either sugar and/or phosphate substitutions, and allows the remaining bases to exhibit their enzymatic activity. The group or compound can be abasic in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine, for example at the C1 position of the sugar.

In one embodiment, the invention features a short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein one or both strands of the siNA molecule that are assembled from two separate oligonucleotides do not comprise any ribonucleotides. All positions within the siNA can include chemically modified nucleotides and/or non-nucleotides such as nucleotides and or non-nucleotides having Formula I, II, III, IV, V, VI, or VII or any combination thereof to the extent that the ability of the siNA molecule to support RNAi activity in a cell is maintained.

In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence. In another embodiment, the single stranded siNA molecule of the invention comprises a 5′-terminal phosphate group. In another embodiment, the single stranded siNA molecule of the invention comprises a 5′-terminal phosphate group and a 3′-terminal phosphate group (e.g., a 2′,3′-cyclic phosphate). In another embodiment, the single stranded siNA molecule of the invention comprises between 19 and 29 nucleotides. In yet another embodiment, the single stranded siNA molecule of the invention comprises one or more chemically modified nucleotides or non-nucleotides described herein. For example, all the positions within the siNA molecule can include chemically-modified nucleotides such as nucleotides having any of Formulae I-VII, or any combination thereof to the extent that the ability of the siNA molecule to support RNAi activity in a cell is maintained.

In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.

In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.

In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are locked nucleic acid (LNA) nucleotides (e.g., wherein all purine nucleotides are LNA nucleotides or alternately a plurality of purine nucleotides are LNA nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.

In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are 2′-methoxyethyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-methoxyethyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-methoxyethyl purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.

In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are purine ribonucleotides (e.g., wherein all purine nucleotides are purine ribonucleotides or alternately a plurality of purine nucleotides are purine ribonucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.

In another embodiment, any modified nucleotides present in the single stranded siNA molecules of the invention comprise modified nucleotides having properties or characteristics similar to naturally occurring ribonucleotides. For example, the invention features siNA molecules including modified nucleotides having a Northern conformation (e.g., Northern pseudorotation cycle, see for example Saenger, Principles of Nucleic Acid Structure, Springer-Verlag ed., 1984). As such, chemically modified nucleotides present in the single stranded siNA molecules of the invention are preferably resistant to nuclease degradation while at the same time maintaining the capacity to mediate RNAi.

E. Preparation of Oligonucleotides

The present oligonucleotides can be prepared by methods available to those skilled in the art. For example, unmodified RNA can be prepared by transcription, e.g., in vitro, using methods and constructs available in the art. The sequence for the particular target, and its complementary sequence can be inserted into a selected vector, and transcribed to produce the desired oligonucleotides by conventional methods.

In many cases, it will be desirable to chemically synthesize the oligonucleotides, e.g., for chemically modified oligonucleotides. Such syntheses are known in the art, and are described, for example, below.

Thus, siNA molecules can be designed to interact with various sites in the RNA message, for example target sequences within the RNA sequences described herein. The sequence of one strand of the siNA molecule(s) is complementary to the target site sequences described above. The siNA molecules can be chemically synthesized using methods described herein. Inactive siNA molecules that are used as control sequences can be synthesized by scrambling the sequence of the siNA molecules such that it is not complementary to the target sequence. Generally, siNA constructs can by synthesized using solid phase oligonucleotide synthesis methods as described herein (see for example Usman et al., U.S. Pat. Nos. 5,804,683; 5,831,071; 5,998,203; 6,117,657; 6,353,098; 6,362,323; 6,437,117; 6,469,158; Scaringe et al., U.S. Pat. Nos. 6,111,086; 6,008,400; 6,111,086). Modification of synthesis conditions can be used to optimize coupling efficiency, for example by using differing coupling times, differing reagent/phosphoramidite concentrations, differing contact times, differing solid supports and solid support linker chemistries depending on the particular chemical composition of the siNA to be synthesized. Deprotection and purification of the siNA can be performed as is generally described in Vargeese et al., U.S. Ser. No. 10/194,875, incorporated by reference herein in its entirety. Additionally, deprotection conditions can be modified to provide the best possible yield and purity of siNA constructs. For example, applicant has observed that oligonucleotides comprising 2′-deoxy-2′-fluoro nucleotides can degrade under inappropriate deprotection conditions. Such oligonucleotides are deprotected using aqueous methylamine at about 35° C. for 30 minutes. If the 2′-deoxy-2′-fluoro containing oligonucleotide also comprises ribonucleotides, after deprotection with aqueous methylamine at about 35° C. for 30 minutes, TEA-HF is added and the reaction maintained at about 65° C. for an additional 15 minutes.

Synthesis of Nucleic Acid Molecules

In greater detail, synthesis of nucleic acids greater than 100 nucleotides in length is difficult using automated methods, and the therapeutic cost of such molecules is prohibitive. In this invention, small nucleic acid motifs, “small” refers to nucleic acid motifs no more than 100 nucleotides in length, preferably no more than 80 nucleotides in length, and most preferably no more than 50 nucleotides in length; e.g., individual siNA oligonucleotide sequences or siNA sequences synthesized in tandem) are preferably used for exogenous delivery. The simple structure of these molecules increases the ability of the nucleic acid to invade targeted regions of protein and/or RNA structure. Exemplary molecules of the instant invention are chemically synthesized, and others can similarly be synthesized.

Oligonucleotides (e.g., certain modified oligonucleotides or portions of oligonucleotides lacking ribonucleotides) are synthesized using protocols known in the art, for example as described in Caruthers et al., 1992, Methods in Enzymology 211, 3-19, Thompson et al., International PCT Publication No. WO 99/54459, Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684, Wincott et al., 1997, Methods Mol. Bio., 74, 59, Brennan et al., 1998, Biotechnol Bioeng., 61, 33-45, and Brennan, U.S. Pat. No. 6,001,311. All of these references are incorporated herein by reference. The synthesis of oligonucleotides makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 2.5 min coupling step for 2′-O-methylated nucleotides and a 45 sec coupling step for 2′-deoxy nucleotides or 2′-deoxy-2′-fluoro nucleotides. Alternatively, syntheses at the 0.2 μmol scale can be performed on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, Calif.) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M=6.6 μmol) of 2′-O-methyl phosphoramidite and a 105-fold excess of S-ethyl tetrazole (60 μL of 0.25 M=15 μmol) can be used in each coupling cycle of 2′-O-methyl residues relative to polymer-bound 5′-hydroxyl. A 22-fold excess (40 μL of 0.11 M=4.4 μmol) of deoxy phosphoramidite and a 70-fold excess of S-ethyl tetrazole (40 μL of 0.25 M=10 μmol) can be used in each coupling cycle of deoxy residues relative to polymer-bound 5′-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation of the trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer include the following: detritylation solution is 3% TCA in methylene chloride (ABI); capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); and oxidation solution is 16.9 mM I₂, 49 mM pyridine, 9% water in THF (PERSEPTIVE™). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H-1,2-Benzodithiol-3-one 1,1-dioxide, 0.05 M in acetonitrile) is used.

Deprotection of the DNA-based oligonucleotides is performed as follows: the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65° C. for 10 min. After cooling to −20° C., the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/3:1:1, vortexed and the supernatant is then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder.

The method of synthesis used for RNA including certain siNA molecules of the invention follows the procedure as described in Usman et al., 1987, J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990, Nucleic Acids Res., 18, 5433; and Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684 Wincott et al., 1997, Methods Mol. Bio., 74, 59, and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 7.5 min coupling step for alkylsilyl protected nucleotides and a 2.5 min coupling step for 2′-O-methylated nucleotides. Alternatively, syntheses at the 0.2 μmol scale can be done on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, Calif.) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M=6.6 μmol) of 2′-O-methyl phosphoramidite and a 75-fold excess of S-ethyl tetrazole (60 μL of 0.25 M=15 μmol) can be used in each coupling cycle of 2′-O-methyl residues relative to polymer-bound 5′-hydroxyl. A 66-fold excess (120 μL of 0.11 M=13.2 μmol) of alkylsilyl (ribo) protected phosphoramidite and a 150-fold excess of S-ethyl tetrazole (120 μL of 0.25 M=30 μmol) can be used in each coupling cycle of ribo residues relative to polymer-bound 5′-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation of the trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer include the following: detritylation solution is 3% TCA in methylene chloride (ABI); capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); oxidation solution is 16.9 mM I₂, 49 mM pyridine, 9% water in THF (PERSEPTIVE™). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H-1,2-Benzodithiol-3-one 1,1-dioxide 0.05 M in acetonitrile) is used.

Deprotection of the RNA is performed using either a two-pot or one-pot protocol. For the two-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65° C. for 10 min. After cooling to −20° C., the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/3:1:1, vortexed and the supernatant is then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder. The base deprotected oligoribonucleotide is resuspended in anhydrous TEA/HF/NMP solution (300 μL of a solution of 1.5 mL N-methylpyrrolidinone, 750 μL TEA and 1 mL TEA•3HF to provide a 1.4 M HF concentration) and heated to 65° C. After 1.5 h, the oligomer is quenched with 1.5 M NH₄HCO₃.

Alternatively, for the one-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 33% ethanolic methylamine/DMSO: 1/1 (0.8 mL) at 65° C. for 15 min. The vial is brought to r.t. TEA•3HF (0.1 mL) is added and the vial is heated at 65° C. for 15 min. The sample is cooled at −20° C. and then quenched with 1.5 M NH₄HCO₃.

For purification of the trityl-on oligomers, the quenched NH₄HCO₃ solution is loaded onto a C-18 containing cartridge that had been prewashed with acetonitrile followed by 50 mM TEAA. After washing the loaded cartridge with water, the RNA is detritylated with 0.5% TFA for 13 min. The cartridge is then washed again with water, salt exchanged with 1 M NaCl and washed with water again. The oligonucleotide is then eluted with 30% acetonitrile.

The average stepwise coupling yields are typically >98% (Wincott et al., 1995 Nucleic Acids Res. 23, 2677-2684). Those of ordinary skill in the art will recognize that the scale of synthesis can be adapted to be larger or smaller than the example described above including but not limited to 96-well format.

Alternatively, the nucleic acid molecules of the present invention can be synthesized separately and joined together post-synthetically, for example, by ligation (Moore et al., 1992, Science 256, 9923; Draper et al., International PCT publication No. WO 93/23569; Shabarova et al., 1991, Nucleic Acids Research 19, 4247; Bellon et al., 1997, Nucleosides & Nucleotides, 16, 951; Bellon et al., 1997, Bioconjugate Chem. 8, 204), or by hybridization following synthesis and/or deprotection.

The siNA molecules of the invention can also be synthesized via a tandem synthesis methodology as described below, where both siNA strands are synthesized as a single contiguous oligonucleotide fragment or strand separated by a cleavable linker which is subsequently cleaved to provide separate siNA fragments or strands that hybridize and permit purification of the siNA duplex. The linker can be a oligonucleotide linker or a non-nucleotide linker. The tandem synthesis of siNA as described herein can be readily adapted to both multiwell/multiplate synthesis platforms such as 96 well or similarly larger multi-well platforms. The tandem synthesis of siNA as described herein can also be readily adapted to large scale synthesis platforms employing batch reactors, synthesis columns and the like.

A siNA molecule can also be assembled from two distinct nucleic acid strands or fragments wherein one fragment includes the sense region and the second fragment includes the antisense region of the RNA molecule.

The nucleic acid molecules of the present invention can be modified extensively to enhance stability by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-fluoro, 2′-O-methyl, 2′-H (for a review see Usman and Cedergren, 1992, TIBS 17, 34; Usman et al., 1994, Nucleic Acids Symp. Ser. 31, 163). siNA constructs can be purified by gel electrophoresis using general methods or can be purified by high pressure liquid chromatography (HPLC; see Wincott et al., supra, the totality of which is hereby incorporated herein by reference) and re-suspended in water.

In another aspect of the invention, siNA molecules of the invention are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors can be DNA plasmids or viral vectors. siNA expressing viral vectors can be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. The recombinant vectors capable of expressing the siNA molecules can be delivered as described herein, and persist in target cells. Alternatively, viral vectors can be used that provide for transient expression of siNA molecules.

Tandem Synthesis of siNA Constructs

Exemplary siNA molecules are synthesized in tandem using a cleavable linker, for example a succinyl-based linker. Tandem synthesis as described herein is followed by a one-step purification process that provides RNAi molecules in high yield. This approach is highly amenable to siNA synthesis in support of high throughput RNAi screening, and can be readily adapted to multi-column or multi-well synthesis platforms.

After completing a tandem synthesis of an siNA oligo and its complement in which the 5′-terminal dimethoxytrityl (5′-O-DMT) group remains intact (trityl on synthesis), the oligonucleotides are deprotected as described above. Following deprotection, the siNA sequence strands are allowed to spontaneously hybridize. This hybridization yields a duplex in which one strand has retained the 5′-O-DMT group while the complementary strand comprises a terminal 5′-hydroxyl. The newly formed duplex behaves as a single molecule during routine solid-phase extraction purification (Trityl-On purification) even though only one molecule has a dimethoxytrityl group. Because the strands form a stable duplex, this dimethoxytrityl group (or an equivalent group, such as other trityl groups or other hydrophobic moieties) is all that is required to purify the pair of oligos, for example by using a C18 cartridge.

Standard phosphoramidite synthesis chemistry is used up to point of introducing a tandem linker, such as an inverted deoxy abasic succinate or glyceryl succinate linker or an equivalent cleavable linker. A non-limiting example of linker coupling conditions that can be used includes a hindered base such as diisopropylethylamine (DIPA) and/or DMAP in the presence of an activator reagent such as Bromotripyrrolidinophosphoniumhexafluororophosphate (PyBrOP). After the linker is coupled, standard synthesis chemistry is utilized to complete synthesis of the second sequence leaving the terminal the 5′-O-DMT intact. Following synthesis, the resulting oligonucleotide is deprotected according to the procedures described herein and quenched with a suitable buffer, for example with 50 mM NaOAc or 1.5M NH₄H₂CO₃.

Purification of the siNA duplex can be readily accomplished using solid phase extraction, for example using a Waters C18 SepPak 1 g cartridge conditioned with 1 column volume (CV) of acetonitrile, 2 CV H2O, and 2 CV 50 mM NaOAc: The sample is loaded and then washed with 1 CV H2O or 50 mM NaOAc. Failure sequences are eluted with 1 CV 14% ACN (Aqueous with 50 mM NaOAc and 50 mM NaCl). The column is then washed, for example with 1 CV H2O followed by on-column detritylation, for example by passing 1 CV of 1% aqueous trifluoroacetic acid (TFA) over the column, then adding a second CV of 1% aqueous TFA to the column and allowing to stand for approx. 10 minutes. The remaining TFA solution is removed and the column washed with H2O followed by 1 CV 1 M NaCl and additional H2O. The siNA duplex product is then eluted, for example using 1 CV 20% aqueous CAN.

Optimizing Activity of the Nucleic Acid Molecules.

Chemically synthesizing nucleic acid molecules with modifications (base, sugar and/or phosphate) can prevent their degradation by serum ribonucleases, which can increase their potency (see e.g., Eckstein et al., International Publication No. WO 92/07065; Perrault et al., 1990 Nature 344, 565; Pieken et al., 1991, Science 253, 314; Usman and Cedergren, 1992, Trends in Biochem. Sci. 17, 334; Usman et al., International Publication No. WO 93/15187; and Rossi et al., International Publication No. WO 91/03162; Sproat, U.S. Pat. No. 5,334,711; Gold et al., U.S. Pat. No. 6,300,074; and Burgin et al., supra; all of which are incorporated by reference herein). All of the above references describe various chemical modifications that can be made to the base, phosphate and/or sugar moieties of the nucleic acid molecules described herein. Modifications that enhance their efficacy in cells, and removal of bases from nucleic acid molecules to shorten oligonucleotide synthesis times and reduce chemical requirements are desired.

There are several examples in the art describing sugar, base and phosphate modifications that can be introduced into nucleic acid molecules with significant enhancement in their nuclease stability and efficacy. For example, oligonucleotides are modified to enhance stability and/or enhance biological activity by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-fluoro, 2′-O-methyl, 2′-O-allyl, 2′-H, nucleotide base modifications (for a review see Usman and Cedergren, 1992, TIBS. 17, 34; Usman et al., 1994, Nucleic Acids Symp. Ser. 31, 163; Burgin et al., 1996, Biochemistry, 35, 14090). Sugar modification of nucleic acid molecules have been extensively described in the art (see Eckstein et al., International Publication PCT No. WO 92/07065; Perrault et al. Nature, 1990, 344, 565-568; Pieken et al. Science, 1991, 253, 314-317; Usman and Cedergren, Trends in Biochem. Sci., 1992, 17, 334-339; Usman et al. International Publication PCT No. WO 93/15187; Sproat, U.S. Pat. No. 5,334,711 and Beigelman et al., 1995, J. Biol. Chem., 270, 25702; Beigelman et al., International PCT publication No. WO 97/26270; Beigelman et al., U.S. Pat. No. 5,716,824; Usman et al., U.S. Pat. No. 5,627,053; Woolf et al., International PCT Publication No. WO 98/13526; Thompson et al., U.S. Ser. No. 60/082,404 which was filed on Apr. 20, 1998; Karpeisky et al., 1998, Tetrahedron Lett., 39, 1131; Earnshaw and Gait, 1998, Biopolymers (Nucleic Acid Sciences), 48, 39-55; Verma and Eckstein, 1998, Annu. Rev. Biochem., 67, 99-134; and Burlina et al., 1997, Bioorg. Med. Chem., 5, 1999-2010; all of the references are hereby incorporated in their totality by reference herein). Such publications describe general methods and strategies to determine the location of incorporation of sugar, base and/or phosphate modifications and the like into nucleic acid molecules without modulating catalysis, and are incorporated by reference herein. In view of such teachings, similar modifications can be used as described herein to modify the siNA nucleic acid molecules of the instant invention so long as the ability of siNA to promote RNAi is cells is not significantly inhibited.

While chemical modification of oligonucleotide internucleotide linkages with phosphorothioate, phosphorodithioate, and/or 5′-methylphosphonate linkages improves stability, excessive modifications can cause some toxicity or decreased activity. Therefore, when designing nucleic acid molecules, the amount of these internucleotide linkages should be minimized. The reduction in the concentration of these linkages should lower toxicity, resulting in increased efficacy and higher specificity of these molecules.

Short interfering nucleic acid (siNA) molecules having chemical modifications that maintain or enhance activity are provided. Such a nucleic acid is also generally more resistant to nucleases than an unmodified nucleic acid. Accordingly, the in vitro and/or in vivo activity should not be significantly lowered. In cases in which modulation is the goal, therapeutic nucleic acid molecules delivered exogenously should optimally be stable within cells until translation of the target RNA has been modulated long enough to reduce the levels of the undesirable protein. This period of time varies between hours to days depending upon the disease state. Improvements in the chemical synthesis of RNA and DNA (Wincott et al., 1995, Nucleic Acids Res. 23, 2677; Caruthers et al., 1992, Methods in Enzymology 211, 3-19 (incorporated by reference herein)) have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability, as described above.

In one embodiment, nucleic acid molecules of the invention include one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) G-clamp nucleotides. A G-clamp nucleotide is a modified cytosine analog wherein the modifications confer the ability to hydrogen bond both Watson-Crick and Hoogsteen faces of a complementary guanine within a duplex, see for example Lin and Matteucci, 1998, J. Am. Chem. Soc., 120, 8531-8532. A single G-clamp analog substitution within an oligonucleotide can result in substantially enhanced helical thermal stability and mismatch discrimination when hybridized to complementary oligonucleotides. The inclusion of such nucleotides in nucleic acid molecules of the invention results in both enhanced affinity and specificity to nucleic acid targets, complementary sequences, or template strands. In another embodiment, nucleic acid molecules of the invention include one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) LNA “locked nucleic acid” nucleotides such as a 2′,4′-C mythylene bicyclo nucleotide (see for example Wengel et al., International PCT Publication No. WO 00/66604 and WO 99/14226).

In another embodiment, the invention features conjugates and/or complexes of siNA molecules of the invention. Such conjugates and/or complexes can be used to facilitate delivery of siNA molecules into a biological system, such as a cell. The conjugates and complexes provided by the instant invention can impart therapeutic activity by transferring therapeutic compounds across cellular membranes, altering the pharmacokinetics, and/or modulating the localization of nucleic acid molecules of the invention. The present invention encompasses the design and synthesis of novel conjugates and complexes for the delivery of molecules, including, but not limited to, small molecules, lipids, phospholipids, nucleosides, nucleotides, nucleic acids, antibodies, toxins, negatively charged polymers and other polymers, for example proteins, peptides, hormones, carbohydrates, polyethylene glycols, or polyamines, across cellular membranes. In general, the transporters described are designed to be used either individually or as part of a multi-component system, with or without degradable linkers. These compounds are expected to improve delivery and/or localization of nucleic acid molecules of the invention into a number of cell types originating from different tissues, in the presence or absence of serum (see Sullenger and Cech, U.S. Pat. No. 5,854,038). Conjugates of the molecules described herein can be attached to biologically active molecules via linkers that are biodegradable, such as biodegradable nucleic acid linker molecules.

The term “biodegradable linker” as used herein, refers to a nucleic acid or non-nucleic acid linker molecule that is designed as a biodegradable linker to connect one molecule to another molecule, for example, a biologically active molecule to a siNA molecule of the invention or the sense and antisense strands of a siNA molecule of the invention. The biodegradable linker is designed such that its stability can be modulated for a particular purpose, such as delivery to a particular tissue or cell type. The stability of a nucleic acid-based biodegradable linker molecule can be modulated by using various chemistries, for example combinations of ribonucleotides, deoxyribonucleotides, and chemically-modified nucleotides, such as 2′-O-methyl, 2′-fluoro, 2′-amino, 2′-O-amino, 2′-C-allyl, 2′-O-allyl, and other 2′-modified or base modified nucleotides. The biodegradable nucleic acid linker molecule can be a dimer, trimer, tetramer or longer nucleic acid molecule, for example, an oligonucleotide of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides in length, or can comprise a single nucleotide with a phosphorus-based linkage, for example, a phosphoramidate or phosphodiester linkage. The biodegradable nucleic acid linker molecule can also comprise nucleic acid backbone, nucleic acid sugar, or nucleic acid base modifications.

The term “biodegradable” as used herein, refers to degradation in a biological system, for example enzymatic degradation or chemical degradation.

The term “biologically active molecule” as used herein, refers to compounds or molecules that are capable of eliciting or modifying a biological response in a system. Non-limiting examples of biologically active siNA molecules either alone or in combination with other molecules contemplated by the instant invention include therapeutically active molecules such as antibodies, hormones, antivirals, peptides, proteins, chemotherapeutics, small molecules, vitamins, co-factors, nucleosides, nucleotides, oligonucleotides, enzymatic nucleic acids, antisense nucleic acids, triplex forming oligonucleotides, 2,5-A chimeras, siNA, dsRNA, allozymes, aptamers, decoys and analogs thereof. Biologically active molecules of the invention also include molecules capable of modulating the pharmacokinetics and/or pharmacodynamics of other biologically active molecules, for example, lipids and polymers such as polyamines, polyamides, polyethylene glycol and other polyethers.

The term “phospholipid” as used herein, refers to a hydrophobic molecule comprising at least one phosphorus group. For example, a phospholipid can comprise a phosphorus-containing group and saturated or unsaturated alkyl group, optionally substituted with OH, COOH, oxo, amine, or substituted or unsubstituted aryl groups.

Therapeutic nucleic acid molecules (e.g., siNA molecules) delivered exogenously optimally are stable within cells until reverse transcription of the RNA has been modulated long enough to reduce the levels of the RNA transcript. The nucleic acid molecules are resistant to nucleases in order to function as effective intracellular therapeutic agents. Improvements in the chemical synthesis of nucleic acid molecules described in the instant invention and in the art have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability as described above.

In yet another embodiment, siNA molecules having chemical modifications that maintain or enhance enzymatic activity of proteins involved in RNAi are provided. Such nucleic acids are also generally more resistant to nucleases than unmodified nucleic acids. Thus, in vitro and/or in vivo the activity should not be significantly lowered.

Use of the nucleic acid-based molecules of the invention will lead to better treatment of the disease progression by affording the possibility of combination therapies (e.g., multiple siNA molecules targeted to different genes; nucleic acid molecules coupled with known small molecule modulators; or intermittent treatment with combinations of molecules, including different motifs and/or other chemical or biological molecules). The treatment of subjects with siNA molecules can also include combinations of different types of nucleic acid molecules, such as enzymatic nucleic acid molecules (ribozymes), allozymes, antisense, 2,5-A oligoadenylate, decoys, and aptamers.

In another aspect a siNA molecule of the invention comprises one or more 5′ and/or a 3′-cap structure, for example on only the sense siNA strand, the antisense siNA strand, or both siNA strands.

By “cap structure” is meant chemical modifications, which have been incorporated at either terminus of the oligonucleotide (see, for example, Adamic et al., U.S. Pat. No. 5,998,203, incorporated by reference herein). These terminal modifications protect the nucleic acid molecule from exonuclease degradation, and may help in delivery and/or localization within a cell. The cap may be present at the 5′-terminus (5′-cap) or at the 3′-terminal (3′-cap) or may be present on both termini. In non-limiting examples: the 5′-cap is selected from the group comprising glyceryl, inverted deoxy abasic residue (moiety); 4′,5′-methylene nucleotide; 1-(beta-D-erythrofuranosyl) nucleotide, 4′-thio nucleotide; carbocyclic nucleotide; 1,5-anhydrohexitol nucleotide; L-nucleotides; alpha-nucleotides; modified base nucleotide; phosphorodithioate linkage; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; acyclic 3,4-dihydroxybutyl nucleotide; acyclic 3,5-dihydroxypentyl nucleotide, 3′-3′-inverted nucleotide moiety; 3′-3′-inverted abasic moiety; 3′-2′-inverted nucleotide moiety; 3′-2′-inverted abasic moiety; 1,4-butanediol phosphate; 3′-phosphoramidate; hexylphosphate; aminohexyl phosphate; 3′-phosphate; 3′-phosphorothioate; phosphorodithioate; or bridging or non-bridging methylphosphonate moiety.

In yet another embodiment, the 3′-cap is selected from a group comprising glyceryl, inverted deoxy abasic residue (moiety), 4′,5′-methylene nucleotide; I-(beta-D-erythrofuranosyl) nucleotide; 4′-thio nucleotide, carbocyclic nucleotide; 5′-amino-alkyl phosphate; 1,3-diamino-2-propyl phosphate; 3-aminopropyl phosphate; 6-aminohexyl phosphate; 1,2-aminododecyl phosphate; hydroxypropyl phosphate; 1,5-anhydrohexitol nucleotide; L-nucleotide; alpha-nucleotide; modified base nucleotide; phosphorodithioate; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; 3,4-dihydroxybutyl nucleotide; 3,5-dihydroxypentyl nucleotide, 5′-5′-inverted nucleotide moiety; 5′-5′-inverted abasic moiety; 5′-phosphoramidate; 5′-phosphorothioate; 1,4-butanediol phosphate; 5′-amino; bridging and/or non-bridging 5′-phosphoramidate, phosphorothioate and/or phosphorodithioate, bridging or non bridging methylphosphonate and 5′-mercapto moieties (for more details see Beaucage and Iyer, 1993, Tetrahedron 49, 1925; incorporated by reference herein).

By the term “non-nucleotide” is meant any group or compound which can be incorporated into a nucleic acid chain in the place of one or more nucleotide units, including either sugar and/or phosphate substitutions, and allows the remaining bases to exhibit their enzymatic activity. The group or compound is abasic in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine and therefore lacks a base at the 1′-position.

An “alkyl” group refers to a saturated aliphatic hydrocarbon, including straight-chain, branched-chain, and cyclic alkyl groups. Preferably, the alkyl group has 1 to 12 carbons. More preferably, it is a lower alkyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkyl group can be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO₂ or N(CH₃)₂, amino, or SH. The term also includes alkenyl groups that are unsaturated hydrocarbon groups containing at least one carbon-carbon double bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkenyl group has 1 to 12 carbons. More preferably, it is a lower alkenyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkenyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO₂, halogen, N(CH₃)₂, amino, or SH. The term “alkyl” also includes alkynyl groups that have an unsaturated hydrocarbon group containing at least one carbon-carbon triple bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkynyl group has 1 to 12 carbons. More preferably, it is a lower alkynyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkynyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO₂ or N(CH₃)₂, amino or SH.

Such alkyl groups can also include aryl, alkylaryl, carbocyclic aryl, heterocyclic aryl, amide and ester groups. An “aryl” group refers to an aromatic group that has at least one ring having a conjugated pi electron system and includes carbocyclic aryl, heterocyclic aryl and biaryl groups, all of which may be optionally substituted. The preferred substituent(s) of aryl groups are halogen, trihalomethyl, hydroxyl, SH, OH, cyano, alkoxy, alkyl, alkenyl, alkynyl, and amino groups. An “alkylaryl” group refers to an alkyl group (as described above) covalently joined to an aryl group (as described above). Carbocyclic aryl groups are groups wherein the ring atoms on the aromatic ring are all carbon atoms. The carbon atoms are optionally substituted. Heterocyclic aryl groups are groups having from 1 to 3 heteroatoms as ring atoms in the aromatic ring and the remainder of the ring atoms are carbon atoms. Suitable heteroatoms include oxygen, sulfur, and nitrogen, and include furanyl, thienyl, pyridyl, pyrrolyl, N-lower alkyl pyrrolo, pyrimidyl, pyrazinyl, imidazolyl and the like, all optionally substituted. An “amide” refers to an —C(O)—NH—R, where R is either alkyl, aryl, alkylaryl or hydrogen. An “ester” refers to an —C(O)—OR′, where R is either alkyl, aryl, alkylaryl or hydrogen.

By “nucleotide” as used herein is as recognized in the art to include natural bases (standard), and modified bases well known in the art. Such bases are generally located at the 1′ position of a nucleotide sugar moiety. Nucleotides generally comprise a base, sugar and a phosphate group. The nucleotides can be unmodified or modified at the sugar, phosphate and/or base moiety, (also referred to interchangeably as nucleotide analogs, modified nucleotides, non-natural nucleotides, non-standard nucleotides and other; see, for example, Usman and McSwiggen, supra; Eckstein et al., International PCT Publication No. WO 92/07065; Usman et al., International PCT Publication No. WO 93/15187; Uhlman & Peyman, supra, all are hereby incorporated by reference herein). There are several examples of modified nucleic acid bases known in the art as summarized by Limbach et al., 1994, Nucleic Acids Res. 22, 2183. Some of the non-limiting examples of base modifications that can be introduced into nucleic acid molecules include, inosine, purine, pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2,4,6-trimethoxy benzene, 3-methyl uracil, dihydrouridine, naphthyl, aminophenyl, 5-alkylcytidines (e.g., 5-methylcytidine), 5-alkyluridines (e.g., ribothymidine), 5-halouridine (e.g., 5-bromouridine) or 6-azapyrimidines or 6-alkylpyrimidines (e.g. 6-methyluridine), propyne, and others (Burgin et al., 1996, Biochemistry, 35, 14090; Uhlman & Peyman, supra). By “modified bases” in this aspect is meant nucleotide bases other than adenine, guanine, cytosine and uracil at 1′ position or their equivalents.

In one embodiment, the invention features modified siNA molecules, with phosphate backbone modifications comprising one or more phosphorothioate, phosphorodithioate, methylphosphonate, phosphotriester, morpholino, amidate carbamate, carboxymethyl, acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, formacetal, thioformacetal, and/or alkylsilyl, substitutions. For a review of oligonucleotide backbone modifications, see Hunziker and Leumann, 1995, Nucleic Acid Analogues: Synthesis and Properties, in Modern Synthetic Methods, VCH, 331-417, and Mesmaeker et al., 1994, Novel Backbone Replacements for Oligonucleotides, in Carbohydrate Modifications in Antisense Research, ACS, 24-39.

By “abasic” is meant sugar moieties lacking a base or having other chemical groups in place of a base at the 1′ position, see for example Adamic et al., U.S. Pat. No. 5,998,203.

By “unmodified nucleoside” is meant one of the bases adenine, cytosine, guanine, thymine, or uracil joined to the 1′ carbon of β-D-ribo-furanose.

By “modified nucleoside” is meant any nucleotide base which contains a modification in the chemical structure of an unmodified nucleotide base, sugar and/or phosphate. Non-limiting examples of modified nucleotides are shown by Formulae I-VII and/or other modifications described herein.

In connection with 2′-modified nucleotides as described for the present invention, by “amino” is meant 2′—NH₂ or 2′-O—NH₂, which may be modified or unmodified. Such modified groups are described, for example, in Eckstein et al., U.S. Pat. No. 5,672,695 and Matulic-Adamic et al., U.S. Pat. No. 6,248,878, which are both incorporated by reference in their entireties.

Various modifications to nucleic acid siNA structure can be made to enhance the utility of these molecules. Such modifications will enhance shelf-life, half-life in vitro, stability, and ease of introduction of such oligonucleotides to the target site, e.g., to enhance penetration of cellular membranes, and confer the ability to recognize and bind to targeted cells.

F. Compositions for Administration

Suitable pharmaceutical compositions containing the present RNAi inducing oligonucleotides can be prepared in many different forms. In most cases, it is desirable to apply the active oligonucleotide topically to one or more hair producing skin areas on a subject. For these applications, a composition that flows, or is spreadable or sprayable is advantageous. Examples of such compositions include, for example, solutions, suspensions, emulsions, lotions, creams, gels, ointments, liposome preparations, and the like. Preparation of such pharmaceutical compositions is well-known in the art, and can be utilized for the present invention.

Thus, the oligonucleotide formulations useful in the present invention will generally include the oligonucleotide(s) and a pharmaceutically acceptable carrier, e.g., any liquid or nonliquid carrier, gel, cream, ointment, lotion, paste, emulsifier, solvent, liquid diluent, powder, or the like, which is stable with respect to all components of the topical pharmaceutical formulation and which is suitable for topical administration of oligonucleotides according to the method of the invention. Such carriers are well known in the art.

A topical carrier, as noted above, is one which is generally suited to topical drug administration and includes any such materials known in the art. The topical carrier is selected so as to provide the composition in the desired form, e.g., as a liquid, lotion, cream, paste, gel, or ointment, and may be comprised of a material of either naturally occurring or synthetic origin. It is essential, clearly, that the selected carrier not adversely affect the oligonucleotide or other components of the topical formulation. Examples of suitable topical carriers for use herein include water, alcohols and other nontoxic organic solvents, glycerin, mineral oil, silicone, petroleum jelly, lanolin, fatty acids, vegetable oils, waxes, and the like. Particularly preferred formulations herein are colorless, odorless ointments, lotions, creams and gels.

Ointments, which are semisolid preparations, are typically based on petrolatum or other petroleum derivatives. As will be appreciated by the ordinarily skilled artisan, the specific ointment base to be used is one that provides for optimum oligonucleotide delivery, and, preferably, provides for other desired characteristics as well, e.g., emolliency or the like. As with other carriers or vehicles, an ointment base should be inert, stable, nonirritating and nonsensitizing. As explained in Remington: The Science and Practice of Pharmacy, 19th Ed. (Easton, Pa.: Mack Publishing Co., 1995), at pages 1399-1404, ointment bases may be grouped in four classes: oleaginous bases; emulsifiable bases; emulsion bases; and water-soluble bases. Oleaginous ointment bases include, for example, vegetable oils, fats obtained from animals, and semisolid hydrocarbons obtained from petroleum. Emulsifiable ointment bases, also known as absorbent ointment bases, contain little or no water and include, for example, hydroxystearin sulfate, anhydrous lanolin and hydrophilic petrolatum. Emulsion ointment bases are either water-in-oil (W/O) emulsions or oil-in-water (O/W) emulsions, and include, for example, cetyl alcohol, glyceryl monostearate, lanolin and stearic acid. Preferred water-soluble ointment bases are prepared from polyethylene glycols of varying molecular weight; again, reference may be had to Remington: The Science and Practice of Pharmacy for further information.

Lotions, which are preparations that are to be applied to the skin surface without friction, are typically liquid or semiliquid preparations in which solid particles, including the oligonucleotide, are present in a water or alcohol base. Lotions are usually suspensions of solids, and preferably, for the present purpose, comprise a liquid oily emulsion of the oil-in-water type. Lotions are preferred formulations for oligonucleotide delivery to large body areas, because of the ease of applying a more fluid composition. It is generally necessary that the insoluble matter in a lotion be finely divided. Lotions will typically contain suspending agents to produce better dispersions as well as compounds useful for localizing and holding the active agent in contact with the skin, e.g., methylcellulose, sodium carboxymethyl-cellulose, or the like.

Creams containing a oligonucleotide for delivery according to the method of the invention are viscous liquid or semisolid emulsions, either oil-in-water or water-in-oil. Cream bases are water-washable, and contain an oil phase, an emulsifier and an aqueous phase. The oil phase, also sometimes called the “internal” phase, is generally comprised of petrolatum and a fatty alcohol such as cetyl or stearyl alcohol; the aqueous phase usually, although not necessarily, exceeds the oil phase in volume, and generally contains a humectant. The emulsifier in a cream formulation, as explained in Remington, supra, is generally a nonionic, anionic, cationic or amphoteric surfactant.

Gel formulations can also be used in connection with the present invention. As will be appreciated by those working in the field of topical drug formulation, gels are semisolid, suspension-type systems. Single-phase gels contain organic macromolecules distributed substantially uniformly throughout the carrier liquid, which is typically aqueous, but also, preferably, contain an alcohol and, optionally, an oil.

The oligonucleotide formulations useful in the invention also encompass sprays, that generally provide the oligonucleotide in an aqueous solution which can be misted onto the skin for delivery. Such sprays include those formulated to provide for concentration of the oligonucleotide solution at the site of administration following delivery, e.g., the spray solution can be primarily composed of alcohol or other like volatile liquid in which the oligonucleotide can be dissolved. Upon delivery to the skin, the alcohol carrier evaporates, leaving concentrated oligonucleotide at the site of administration.

The oligonucleotide formulations useful in the invention can also contain other optional such as opacifiers, anti-oxidants, gelling agents, thickening agents, stabilizers, and the like. Other agents may also be added, such as antimicrobial agents, antifungal agents, antibiotics and anti-inflammatory agents such as steroids.

The oligonucleotide formulations can include other components that, while not necessary for delivery of oligonucleotides to the skin, may enhance such delivery. For example, although it is not necessary to the practice of the invention, the oligonucleotide formulations may also contain a skin permeation enhancer. Suitable enhancers are well know in the art and include, for example, dimethylsulfoxide (DMSO), dimethyl formamide (DMF), N,N-dimethylacetamide (DMA), decylmethylsulfoxide (C.sub.10 MSO), C.sub.2-C.sub.6 alkanediols, and the 1-substituted azacycloheptan-2-ones, particularly 1-n-dodecylcyclazacycloheptan-2-one (available under the trademark Azone® from Whitby Research Incorporated, Richmond, Va.), alcohols, and the like. Preferably, the oligonucleotides delivered are substantially free of such permeation enhancers.

The additional components should not substantially interfere with the integrity or biological activity of the oligonucleotide or the formulation in which it is provided, i.e., the additional components do not adversely affect the uptake of the oligonucleotide by skin cells or chemically modify the oligonucleotide in an undesirable manner.

It will be recognized by those skilled in the art that the optimal quantity and spacing of individual dosages of oligonucleotides will be determined by the precise form and components of the oligonucleotide formulation to be delivered, the site of administration, the use to which the delivery device is applied (e.g., immunization, treatment of a condition, production of transgenic animals, etc.), and the particular subject to which the oligonucleotide formulation is to be delivered, and that such optimums can be determined by conventional techniques. It will also be appreciated by one skilled in the art that the optimal dosing regimen, i.e., the number of doses of oligonucleotides, can be ascertained using conventional methods, e.g., course of treatment determination tests. Generally, a dosing regimen will involve administration of the selected oligonucleotide formulation at least once daily, and may be one to four times daily or more.

The practice of the present invention will employ, unless otherwise indicated, conventional techniques of drug formulation, particularly topical drug formulation, which are within the skill of the art. Such techniques are fully explained in the literature. See Remington: The Science and Practice of Pharmacy, cited supra, as well as Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Ed. (New York: McGraw-Hill, 1996).

Dosage Forms of the Oligonucleotide Formulations

The oligonucleotides can be prepared in unit dosage form (e.g., in ampules), or in multidose form. The oligonucleotides may be present in such forms as suspensions, solutions, gels, or creams, preferably in an aqueous vehicle (e.g., in a buffered solution). Alternatively, the oligonucleotide salt may be in lyophilized form for reconstitution, at the time of delivery, with a suitable vehicle, such as sterile pyrogen-free water or phosphate-buffered saline (PBS). Both liquid as well as lyophilized forms that are to be reconstituted preferably comprise agents, preferably buffers, in amounts necessary to suitably adjust the pH of the solution. Nonionic materials, such as sugars, are preferred for adjusting tonicity, and sucrose is particularly preferred. Any of these forms may further comprise suitable formulatory agents, such as starch or sugar, glycerol or saline. The compositions per unit dosage, whether liquid, gel, cream, or solid, may contain from 0.1% to 99% of oligonucleotide material.

Delivery Devices

The oligonucleotide formulation can administered using and be provided within, a delivery device (e.g., a patch, bandage, etc.) that provides for both maintenance of contact between the skin of the subject and the oligonucleotide formulation and substantially uninhibited movement of the oligonucleotide into the skin. The delivery device generally does not in and of itself facilitate movement of the oligonucleotide contained therein into the skin, but rather primarily acts to ensure that the oligonucleotide formulation is in contact with the skin for a time sufficient to allow genetic alteration of skin cells. The delivery device comprises a delivery means, or “reservoir,” which is saturated with a formulation that comprises an amount of oligonucleotide sufficient to genetic alteration of skin cells to which it is to be delivered and sufficient to elicit the desired biological effect. For example, where the delivery device is to be used to deliver a oligonucleotide for genetic immunization of a human, the delivery means of the device preferably contains an amount of oligonucleotide ranging from about 10 .mu.g to about 1,000 .mu.g, preferably from about 100 .mu.g to about 500 .mu.g.

Suitable delivery means of the delivery devices of the invention include, but are not limited to, sponges, hydrogels, and absorptive materials (e.g., gauze) that allow for retention of the oligonucleotide formulation at the site of oligonucleotide administration without substantially interfering with the delivery of oligonucleotide to the skin. It is important that, upon contact of the delivery means with the skin, the oligonucleotides contained in the delivery means diffuse or otherwise pass from the delivery means into the skin at a rate and in an amount suitable to accomplish the desired effect.

In general, the delivery means has at least two surfaces: a first surface that serves as a skin-contacting surface; and a second surface opposite the skin-contacting surface. Preferably, the second surface is in contact with a liquid-impermeable coating that substantially prevents movement of the oligonucleotide out of the delivery means through the second surface (e.g., in a direction away from the first skin-contacting surface). Preferably, the liquid-impermeable coating also decreases the rate of dehydration of the oligonucleotide formulation contained in the delivery means. In one embodiment, the first skin-contacting surface of the delivery means is associated with a liquid-impermeable, removable layer (e.g., release liner), which layer is removed just prior to placement of the first surface on the skin of a subject for administration of the oligonucleotide.

The delivery device preferably comprises an adhesive means, which can be a polymeric matrix of a pharmaceutically acceptable contact adhesive material, which serves to affix the system to the skin during drug delivery. The adhesive means facilitates retention of the delivery means on the skin at the desired site of administration. Preferably, the adhesive means comprises an adhesive substance that allows for retention of the delivery means at the desired site for a selected amount of time, but additionally allows for easy removal of the delivery means without substantially adversely affecting the skin with which the adhesive substance was in contact.

The adhesive substance used must be biocompatible with the skin of the subject, and should not substantially interfere with the delivery of oligonucleotide to the subject. Examples of suitable skin contact adhesive materials include, but are not limited to, polyethylenes, polysiloxanes, polyisobutylenes, polyacrylates, polyurethanes, and the like. The particular polymeric adhesive selected will depend on the particular oligonucleotide formulation, vehicle, etc., i.e., the adhesive must be compatible with all components of the oligonucleotide formulation.

In one embodiment, the delivery means and skin contact adhesive are present as separate and distinct layers of the delivery device, with the adhesive underlying the delivery means which, in this case, may be either a polymeric matrix as described above, or it may be a liquid or hydrogel reservoir, or may take some other form. In another embodiment, the delivery means is an adhesive bandage. Exemplary delivery devices suitable for use in the invention include, but are not limited to, those devices described in U.S. Pat. No. 5,160,328; U.S. Pat. No. 5,254,346; U.S. Pat. No. 5,714,162; U.S. Pat. No. 5,667,798; U.S. Pat. No. 5,230,896; and U.S. Pat. No. 5,260,066. Methods for preparation of suitable delivery means and other elements associated with the delivery means, such as an adhesive means are well known in the art.

In another embodiment, the oligonucleotide formulation of the invention is provided as a patch, wherein the drug composition is contained within, for example, a laminated structure that serves as a drug delivery device to be affixed to the skin. In such a structure, the oligonucleotide composition is contained within a delivery means, or “reservoir,” which lies beneath an upper backing layer. The laminated structure may contain a single reservoir, or it may contain multiple reservoirs.

The backing layer in the laminates of the patch, which serves as the upper surface of the delivery device, functions as the primary structural element of the laminated structure and provides the device with much of its flexibility. The material selected for the backing material should be selected so that it is substantially impermeable to oligonucleotide and, preferably, to other components of the oligonucleotide formulation, thus preventing loss of any components through the upper surface of the device, and preferably substantially impeding dehydration of the composition in the reservoir. The backing layer may be either occlusive or nonocclusive, depending on whether it is desired that the skin become hydrated during drug delivery. The backing is preferably made of a sheet or film of a preferably flexible elastomeric material. Examples of polymers that are suitable for the backing layer include polyethylene, polypropylene, polyesters, and the like.

During storage and prior to use, the laminated structure includes a release liner. Immediately prior to use, this layer is removed from the device to expose the skin-contacting surface of the device, which as noted above may be either the reservoir itself or a separate contact adhesive layer, so that the system may be affixed to the skin. The release liner is preferably made of a material that is substantially impermeable to the oligonucleotide and other components in the oligonucleotide formulation.

Delivery devices suitable for use in the present invention may be fabricated using conventional techniques, known in the art, for example by casting a fluid admixture of adhesive, oligonucleotide, and carrier/vehicle onto the backing layer, followed by lamination of the release liner. Similarly, the adhesive mixture may be cast onto the release liner, followed by lamination of the backing layer. Alternatively, the oligonucleotide reservoir may be prepared in the absence of oligonucleotide formulation or excipient, and then loaded by “soaking” in a drug/vehicle mixture.

As with the topical formulations of the invention, the oligonucleotide formulation contained within the delivery means of the delivery devices may contain a number of components. Furthermore, such delivery devices can be used in connection with administration of any of the oligonucleotide formulations described herein, e.g., naked oligonucleotide formulations, or lipid- or liposome-comprising oligonucleotide formulations. Regardless of the specific basic components of the oligonucleotide formulation, the oligonucleotide formulation will generally dissolved, dispersed or suspended in a suitable pharmaceutically acceptable vehicle, typically an aqueous solution or gel. Other components that may be present include preservatives, stabilizers, and the like.

Packaging of the Oligonucleotide Formulations and Delivery Devices

The units dosage ampules, multidose containers, and/or delivery devices (e.g., patches) in which the oligonucleotides are packaged prior to use may comprise an hermetically sealed container enclosing an amount of oligonucleotide or oligonucleotide formulation containing a oligonucleotide suitable for a pharmaceutically effective dose thereof, or multiples of an effective dose. The oligonucleotide is preferably packaged as a sterile formulation, and the hermetically sealed container is designed to preserve sterility of the formulation until use. Where the oligonucleotides are provided in a patch-style delivery device, the patches may be contained in a strip of individually separable packaged patches for ease in dispensing.

The container in which the oligonucleotide formulation and/or delivery device is packaged is labeled, and the label bears a notice in the form prescribed by any appropriate governmental agency. For example, where the oligonucleotides are to be administered to humans, the package comprises a notice that reflects approval by the Food and Drug Administration under the applicable federal law, of the manufacture, use, or sale of the oligonucleotide material therein for human administration. Federal law requires that the use of pharmaceutical agents in the therapy of humans be approved by an agency of the Federal government. Responsibility for enforcement is the responsibility of the Food and Drug Administration, which issues appropriate regulations for securing such approval, detailed in 21 U.S.C. 301-392. Regulation for biologic material, comprising products made from the tissues of animals is provided under 42 U.S.C 262. Similar approval is required by most foreign countries. Regulations vary from country to country, but the individual procedures are well known to those in the art.

Introduction of Oligonucleotides into Skin Cells According to the Method of the Invention

Application of the Oligonucleotide to Skin

Administration of the oligonucleotide is accomplished by contacting a oligonucleotide-comprising formulation (e.g., a buffered salt solution comprising the oligonucleotide) with an area of skin for a time sufficient to allow genetic alteration of skin cells. Preferably, the oligonucleotide is applied to hirsute skin. The oligonucleotide can be applied to skin without substantial pretreatment or with pretreatment, preferably without pretreatment of the skin. “Pretreatment” can generally encompass removal of hair from the skin, increasing skin permeability by mechanical means (e.g, abrasion), increasing skin permeability by application of a chemical agent to the site either before or during oligonucleotide administration, and application of an irritant or other like chemical agent to elicit a non-specific immune response or an immune response toward the irritant (e.g., by application of a keratinolytic agent). Administration of the oligonucleotide can be accomplished according to the invention without the application of an electric field or electric pulse (e.g., as in iontophoresis), without breaking the skin (e.g., by abrasion or through use of a needle), and without application of pressure to the site of administration (e.g., via jet propulsion, pressurized air, etc.). Furthermore, oligonucleotide administration can be accomplished using a oligonucleotide formulation that is substantially free of permeabilizing agents, detergents, or other chemical agents that facilitate entry of the oligonucleotide into the skin.

Once the oligonucleotide-comprising formulation is brought into contact with skin, contact is maintained for a time sufficient to allow movement of the oligonucleotide from the formulation into skin and into skin cells. In general, the time of contact between the oligonucleotide and the skin will be at least about 1 min to about 1 hr or more, preferably at least about 30 min. Because there is substantially no toxicity associated with contacting the oligonucleotide with the skin, the time of contact maintained between the oligonucleotide and the skin to which the oligonucleotide is to be delivered is limited only by such factors as the ability to keep the oligonucleotide in a suitable delivery form (e.g., a time during which the oligonucleotide-comprising solution can be prevented from dehydrating) and the ability to physically maintain contact between the oligonucleotide and the site of delivery (e.g., maintenance of a patch comprising the oligonucleotide(s) on the skin). Therefore, the time of contact of a single dose can be as long as several hours to several days, and may be weeks or more. Furthermore, the time of delivery can be further extended by additional subsequent applications of the oligonucleotide to the same or different delivery site on the skin.

While an ethanolic/propylene glycol solution of anti-hairless oligonucleotide as found to deliver beneficial amounts of oligonucleotide to the hair follicle and result in inhibition of hairless, other formulations can also advantageously be used. In particular, liposome compositions can be advantageous. Liposomes were introduced first in about 1980 for topical drug delivery and have since attracted considerable interest due to their potential utility both as a drug carrier and a reservoir for controlled release of drugs within various layers of the skin and the hair follicle. In addition to reducing the undesirable high systemic absorption of topically applied drugs, the major advantage of liposomes compared to other formulations such as ointments or creams, is based on their ability to create a depot, from which the drug is slowly released. The delivery agents also provide advantages in that they protect oligonucleotides against degradation, increase cellular uptake, and may target the drug to specific cells or tissue compartment. Thus, a delivery system allowing the controlled and sustained release of oligonucleotides in vivo can greatly increase the efficacy of gene inhibition technology.

One of the most favored sites of liposome penetration is into the hair follicle, since the hair canal opens directly onto the surface of the skin. Liposomes applied to cultured hair follicles are easily detected in cells lining the inner root sheath. (Li et al., 1992b, In Vitro Cell Dev Biol 28A:679-681.) Liposomes also find their way into the pilosebaceous unit once traveling down the root sheath. (Lieb et al. 1992, J Invest Dermatol 99:108-113.) Liposomes have been shown to direct compounds into the sebaceous gland, when they would otherwise be trapped in the stratum corneum. (Bernard et al., 1997, J Pharm Sci 86:573-578.) Liposomes function both as a controlled release system and as a delivery system transporting encapsulated substances into cells. After topical application, and upon drying, the liposomes develop into a structured film that fills the follicular openings, intimately mixing with the follicular contents, and fostering drug diffusion to the depths of the follicles.

A number of different compositions of liposomes have been tested for in vivo oligonucleotide delivery. For example, three different lipids were compared: N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium chloride (DOTMA), 2,3-dioleyloxy-N-[2(sperminecarboxamido) ethyl]-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA) and N-(1-(2,3-dimyristyloxypropyl)-N,N dimethyl-(2-hydroxyethyl) ammonium bromide (DMRIE). The macrophages incorporated tenfold more oligonucleotide when delivered in conjunction with DOSPA than with the other cationic lipids.

Liposome preparation and encapsulation of oligonucleotides are available from commercial manufacturer, e.g., BioZone Laboratories, Inc. Pittsburg, Calif., which manufactures a wide range of topically applied LipoCeutical products that include cationic lipids.

In addition to cationic lipid liposomes, other types of liposomes can also be used, e.g. pH-sensitive liposomes. The cellular uptake of liposomes passes mainly through an endocytic pathway, and occasionally, liposomes and their contents inadvertently arrive in the lysosomes where they are degraded. The quantity of oligonucleotides that can avoid degradation and reach their nuclear or cytoplasmic target is probably very low. To overcome lysosomal degradation and in order to increase the efficiency of delivery, pH sensitive fusogenic liposomes have been used. These consist of a non-bilayer-forming lipid such as dioleylphosphatidylethanolamine (DOPE) and a titratable acidic amphiphile such as oleic acid (OA) or cholesterylhemisuccinate (CHEMS). (DeOliveira et al., 1998, Biochim. Biophys. Acta Biomembr. 1372:301-310.) At pH 7, the amphiphile maintains the lipid mix in a bilayer (liposome) structure. However, as the complex moves through the endosomes, the pH drops and the amphiphile becomes protonated. This causes the liposome to collapse resulting in fusion with the endosomal membrane and release of the liposome contents into the cytoplasm. However, the anionic nature of pH-sensitive liposomes may lead to poor encapsulation of ODNs. (Hughes et al., 2000, Methods Enzymol 313:342-358.).

As one alternative to liposomes, other carriers/delivery agents can be used, such as cationic polymers. The most widely studied polymers are polylactides and co-polymers of lactic acid and glycolic acid P(LA-GA) and both of these have been evaluated for the use for delivery of oligonucleotides. (Lewis et al., 1998, J Drug Target 5:291-302; Hudson et al., 1999, Int J Pharm 182:49-58.)

In addition to the above, certain patents have described methods for delivery that can be used in the present invention. Examples include the following.

Li and Lishko, U.S. Pat. No. 5,914,126 (incorporated herein by reference in its entirety) describes methods to deliver macromolecules to hair follicles, where the method involves applying to the skin a formulation that includes a macromolecule, such as a nucleic acid, in a liposomal formulation, such that the liposomes target the macromolecule selectively into hair follicle cells by transfer into the follicle without entry into the circulation of the adjacent skin tissue.

Khavari et al., U.S. Pat. No. 6,087,341 (incorporated herein by reference in its entirety) describes methods and compositions for introduction of nucleic acid into skin cells by topical application.

Li and Baranov, U.S. Pat. No. 6,080,127 (incorporated herein by reference in its entirety) describes a skin vibration method for topical targeted delivery of beneficial agents into hair follicles. The vibration frequency can, for example, be about 1 Hz to 100 Hz.

In some applications, it may be useful to include transdermal penetration enhancers, for example, as described in Karande et al., 2004, Nature Biotech. 192-197. As described, two types of compositions were particularly effective. One included sodium laureth sulfate (SLA) with phenyl piperazine (PP). In a particular composition the SLA:PP was as 0.5% (w/v) with the weight ration of SLA=0.7 in the combination. The second included N-lauroyl sarcosine (NLS) with sorbitan monolaurate (S20). In a particular composition, the combination was at 1.0% (w/v) with the weight ration of NLS=0.6.

G. Administration

The present compositions can be administered in various ways, e.g., depending on the condition to be treated, and the type of composition to be used. In many cases, topical administration will be used. This mode of administration is particularly suitable for local hair removal.

In some applications, hair removal is desired in only a portion of the skin area of a subject. In those cases, the composition can be applied locally.

Exemplary Topical Application Methods

Spreading

In most cases, the composition containing the RNAi inducing oligonucleotides will be spread or wiped on the treatment area to form a thin film. Thus, for example, for any of the forms of liquid suspension or solution, cream, lotion, gel, or ointment, a quantity of the composition is spread on the treatment surface or surfaces of the subject, and left for a time to allow oligonucleotides (which may be in a carrier species such as in liposomes, to migrate to the hair follicles.

Spraying

For compositions that are sufficiently liquid, the composition can be sprayed on the treatment site, either with or without protection against overspray on surrounding areas. For spray applications, it may be desirable to protect against inhalation of sprayed material, e.g., by using masks that will filter out the relevant sized aerosol particles.

Injection

In some applications, it will be desirable to remove only specific hairs. Thus, rather than contacting a particular area, a composition will be delivered to one or more particular hair follicles. Such individual follicle delivery can be accomplished in various ways. For example, a drop of liquid containing the active oligonucleotide(s) can be deposited on the hair shaft, and allowed to migrate down the shaft to the follicle. In another approach, a needle can be inserted in the hair channel, and liquid or other composition deposited at or near the follicle.

Application Site Preparation and Hair Cycle Synchronization

In some cases, the present compositions can be applied without any special preparation of the application site. In other cases, however, it is advantageous to prepare the site, e.g., by preliminary removal of hair from the site and/or to combine the present invention with a supplementary method of hair removal. Such removal can be beneficial in several different ways. For example, such removal can reduce the amount of active agent required for the present invention because the material will not be lost by adhering to the hair, and instead will be available for absorption/migration to the hair follicles.

Such removal can also be beneficially be used to supplement the present invention by removing residual hairs. Depending on the manner and amount of RNAi inducing oligonucleotide delivered to the hair follicles, some of the follicles may not be sufficiently inhibited, such that some hairs may grow in the treated area and/or some hairs may be reduced in thickness or length but still present. In such cases, a supplementary method of hair removal can be used to produce a desired level of hair removal, e.g., shaving, chemical depilation, enzymatic hair removal; laser treatment; electrolysis. Certain embodiments of the present invention include such an supplemental method.

It can also be advantageous to synchronize hair cycles in the treatment area. Such synchronization can advantageously be done prior to application of the present compositions, or during an interval of treatment with the present compositions, or in an interval between two occasions or intervals of application of the present compositions.

Such synchronization can be accomplished, for example, by pulling hairs from the follicles (either individually or in larger numbers). Examples of methods for pulling the hairs include plucking and waxing. In some circumstances it will be necessary/desirable to induce follicle synchrony by molecular means. In these instances, skin is treated with a known follicle growth inducer such as cyclosporin A, TPA, Noggin, estrogen receptor agonist, and the like.

In general, if a hair is pulled from a follicle in anagen, that follicle goes into catagen; if a hair is pulled from a follicle in telogen, the follicle is stimulated to produce hair, and thus goes into anagen. Thus, for a more extensive effect using the present invention, a distribution of hairs in anagen, catagen, and telogen can be synchronized in catagen, with one pulling to push anagen follicles to catagen, and two pullings to stimulate telegen follicles to anagen, and then push the newly anagen follicles to catagen. Depending on the reaction of the follicles, such procedure can produce a single phase synchrony, or a two phase synchrony.

EXAMPLE 1

In Vitro siRNA Inhibition of Hairless mRNA

siRNAs were commercially obtained from Ambion, Inc. for human and mouse hairless genes. These are validated, chemically synthesized siRNAs, that are HPLC purified, annealed and ready to use, and guaranteed to reduce target gene expression by 70% or more. For both human and mouse transcripts, two different siRNAs were used. The sequence of the hairless siRNAs is given in the following table. In this and the subsequent tables in this example, upper case letter are used to refer to the human homologs, and lower case letter refer to the mouse homologs of the specified genes.

List of Pre-Designed siRNAs Used for Gene Silencing Experiments.

siRNA	Sense Sequence	Antisense Sequence
HR#1	5′-GGACAUGCUCCCACUUGUGtt-3′	5′-CACAAGUGGGAGCAUGUCCtt-3′
	(SEQ ID NO: 11355)	(SEQ ID NO: 11356)
HR#2	5′-GGAGGCCAUGCUUACCCAUtt-3′	5′-AUGGGUAAGCAUGGCCUCCtt-3′
	(SEQ ID NO: 11357)	(SEQ ID NO: 11358)
hr#1	5′-GGACACACUCUCACUGGUGtt-3′	5′-CACCAGUGAGAGUGUGUCCtt-3′
	(SEQ ID NO: 11359)	(SEQ ID NO: 11360)
hr#2	5′-GGGCUUUUACCACAAGGAUtt-3′	5′-AUCCUUGUGGUAAAAGCCCtt-3′
	(SEQ ID NO: 11361)	(SEQ ID NO: 11362)

We also used siRNAs for the mouse glyceraldehyde-3-phosphate dehydrogenase (gapdh) gene, Silencer™ GAPDH siRNA (Cat no. 4605, Ambion, Inc. Austin, Tex.) as controls to monitor and optimize siRNA experiments.

Human HaCaT, HeLa and mouse NIH 3T3 cells were used in siRNA transfection experiments. Cells were plated on 6-well tissue culture plates in Dulbecco's Modified Eagle Media (D-MEM, Cat no. 10569-010, Invitrogen Corp., Carlsbad, Calif.) with 10% Fetal Bovine Serum (Cat no. 16000-044, Invitrogen, Corp.) so that they were 30-50% confluent at the time of transfection. Immediately before the transfection, the cells were washed in Opti-MEM I Reduced Serum Medium (Cat no. 31985-070, Invitrogen, Inc.). We used 200 μmol of short interfering RNA (siRNA) for each well and the Oligofectamine™ reagent. The transfections were performed according to the manufacturer's instructions (Cat no. 12252-011, Invitrogen, Inc).

Total RNA was isolated 24 and 48 hours post-transfection using the RNeasy Mini Kit (Cat no. 74104, QIAGEN, Inc., Valencia, Calif.) according to the manufacturer's instructions. cDNA synthesis was performed using the SuperScript First-Strand Synthesis System for RT-PCR kit (Cat no. 11904-018, Invitrogen, Corp.) and oligo (dT) primers. Gene activity was determined by the Real-Time quantitative RT-PCR (qRT-PCR) technique.

Real Time Quantitative RT-PCR (qRT-PCR)

Real-Time qRT-PCR was performed using MJ Research Opticon 2 continuous fluorescence detector. For qRT-PCR 40 ng of cDNA obtained from cultured HaCaT, HeLa, and NIH3T3 cells (siRNA treated and untreated), was amplified using the MJ Research DyNAmo Hot Start SYBR Green qPCR kit (Cat no. F-410L, MJ Research, Inc., Waltham, Mass. The DyNAmo Hot Start SYBR Green qPCR kit is a master mix of a modified hot start DNA polymerase with SYBR Green I and the appropriate buffers, all of which have been optimized for real-time quantitative analysis with the MJ Research Opticon 2. PCR amplification of cDNA samples was performed in 96 well optical plates under the following conditions:

1.  Incubate at 95.0 C. tor 00:10:00
2.  Incubate at 95.0 C. for 00:00:20
3.  Incubate at 55.0 C. for 00:00:30
4.  Incubate at 72.0 C. for 00:00:40
5.  Plate Read
6.  Incubate at 77.0 C. for 00:00:01
7.  Plate Read
8.  Go to line 3 for 39 more times
9.  Incubate at 72.0 C. for 00:05:00
10. Melting Curve from 65.0 C. to 95.0 C.
    read every 0.2 C. hold 00:00:01
11. Incubate at 72.0 C. for 00:05:00
END

The list of PCR primers used for Real Time PCR amplifications is given in the following table.

PCR primers used for Real-Time RT-PCR amplifications of mouse and human hairless, mouse glyceraldehyde-3-phosphate dehydrogenase gene, and hypoxanthine guanine phosphoriboxyltransferase 1 (hprt). (HPRT was used as a normalizing internal control in mouse cells the same way GAPDH was used for the human cell lines.)

Gene	Forward primer	Reverse primer
Hr	5′-TTCTACCGCGGTCAAACTCT-3′	5′-TTGGTGTCAGGGATCCAAAG-3′
	(SEQ ID NO: 11363)	(SEQ ID NO: 11364)
GAPDH	5′-AGCCACATCGCTCAGAACAC-3′	5′-GAGGCATTGCTGATGATCTTG-3′
	(SEQ ID NO: 11365)	(SEQ ID NO: 11366)
hr	5′-ACATCAAAGAAGAGACCCCAG-3′	5′-TTCGCACTGGTGACAATGGAA-3′
	(SEQ ID NO: 11367)	(SEQ ID NO: 11368)
gapdh	5′-GTGAACGGATTTGGCCGTATT-3′	5′-TTTTGGCTCCACCCTTCAAGT-3′
	(SEQ ID NO: 11369)	(SEQ ID NO: 11370)
hplt	5′-CCCTGGTTAAGCAGTACAGC-3′	5′-CAGGACTAGAACACCTGCTAA-3′
	(SEQ ID NO: 11371)	(SEQ ID NO: 11372)

Plate readings for fluorescence levels are taken at two steps, 5 and 7. These values indicate the relative amounts of amplicon per well at a particular cycle. The raw numbers obtained from these readings were used to determine the PCR amplification efficiency. This is the measurement of fold amplification per PCR cycle, and is expressed as a fraction or percentage relative to perfect doubling. A PCR resulting in perfect doubling would exhibit 100% amplification efficiency. All of the calculations are done using the LinRegPCR program by J. M. Ruijter and C. Ramakers. The crossing threshold for the experiment is determined manually and is defined at the cycle at which amplification for all samples becomes logarithmic. The relative fold for each amplicon is then determined using the amplification efficiency and crossing threshold for that particular amplicon and normalizing it against the relative starting amounts, which is determined by the GAPDH amplification efficiency and crossing threshold that corresponds to that sample. This is done using parameters and equations set by Lui and Saint (Analytical Biochemistry 302, 52-59 (2002)). The final values can then be used to compare the fold differences in gene expression of a particular gene across several different samples or conditions.

This technique and analysis can be applied to determine the levels of hairless expression, or more specifically, the efficiency of gene silencing using hairless siRNA through comparison of the treated and untreated cell populations.

The following table shows the percentage of gene silencing observed following siRNA treatment of human HeLa and HaCaT cells. Total RNA was collected 48 hours following transfection with siRNAs for hairless (Hr) gene. Gene activity was assayed by real-time quantitative RT-PCR (qRT-PCR) technique. Percent knockdown is calculated by obtaining the ratio of the normalized level of Hr expression in treated and untreated cell populations and subtracting this value from 1 (100% expression).

	Gene
	Expression	Cell	Percent	RNA isolation
siRNA	Tested	Type	Knockdown	time point
HR#1	Hr	HeLa	97.3%	48 hours
HR#2	Hr	HeLa	98.7%	48 hours
HR#2	Hr	HaCaT	95.8%	48 hours

The following table shows the percentage of gene silencing observed following siRNA treatment of mouse NIH3T3 cells. Total RNA was collected 48 hours following transfection with siRNAs for hairless (hr) and glyceraldehyde-3-phosphate dehydrogenase (gpdh) genes. Gene activity was assayed by real-time quantitative RT-PCR (qRT-PCR) technique. Percent knockdown is calculated by obtaining the ratio of the normalized level of hr and gapdh expression in treated and untreated cell populations and subtracting this value from 1 (100% expression).

	Gene
	Expression	Cell	Percent	RNA isolation
siRNA	Tested	Type	Knockdown	time point
hr#1	Hr	NIH3T3	99.3%	48 hours
hr#2	Hr	NIH3T3	99.17%	48 hours
Gapdh	Gapdh	NIH3T3	99.3%	48 hours

EXAMPLE 2

In Vivo Testing: A Phase 1 Clinical Trial of Anti-Hairless siRNA

The goal of this study is to establish the safety of topical application of anti-hairless siRNA (Trichozyme) in healthy human subjects at a dose of 10 μg daily, administered over a period of 3 months.

Inhibition of gene expression using or siRNA technology is a recently developing area of therapy. Several recent studies indicate the usefulness of such therapeutic strategies in a number of different conditions. Our preliminary in vivo studies demonstrated the inhibition of hairless mRNA can be used to permanently inhibit hair growth in experimental animals. Briefly, they inhibit translation from the mRNA transcript originating from the human hairless gene, the first known gene participating in the regulation of the human hair cycle as identified by our group earlier, preventing the synthesis of functional hairless protein. Presence of hairless protein is necessary for uninterrupted hair cycling, and lack of hairless gene expression due to a deleterious mutation or temporary inhibition leads to a permanent inhibition of hair growth and the involution of hair follicles as evidenced by our own in vivo trials in animal models. The successful translation of the result of animal studies to human application leads to a strategy to obtain permanent inhibition of hair growth by temporary topical treatment with Trichozyme.

Study Design

This will be an open label, uncontrolled, safety study. Monitoring for side effects, alterations in hematology, serum chemistries and urine analysis will continue during the 3 month treatment period as well as during the 6 month follow up period after the application is stopped. Subjects will be seen daily by Study personnel during the treatment period and monthly during the follow-up period. The Study will not offer treatment of any side effects that develop.

We will enlist 20 subjects, 10 of which will be treated with the siRNA in an isopropranol or liposomal based vehicle, the other 10 subject will receive treatment with vehicle only. Hair from the dorsal surface of the left forearm will be removed by waxing before applying treatment during the first 30 days of the study. Treatment will consist of topical application of an isopropranol based solution alone or containing anti-hairless siRNA over a 15 cm² area of the dorsal surface of the left forearm using a glass rod. Ample time will be left for absorption.

Subjective side effects, alterations in serum chemistry, hematology and urine analysis will be monitored as well as serum and urine isopropranol level and presence of Trichozymes in serum and urine samples. Photography of the treatment area and hair count will be performed during the initial visit and weekly afterwards during the treatment period of the study then monthly during the follow-up period of the study.

Study Procedures

Before entering in the study subjects will sign an informed consent for disclosure of medical records. A screening questionnaire will be completed as well as a review of medical records to exclude any preexisting medical conditions affecting hair growth or other preexisting diseases listed as exclusion criteria.

Laboratory evaluation—Fasting blood and urine samples will be obtained for the following tests: (a) Hematology—hemoglobin and hematocrit, CBC with differential and platelet count, (b) Serum Chemistry—sodium, total bilirubin, potassium, glucose, chloride, alkaline phosphatase, calcium, AST, ALT, inorganic phosphorus, BUN, creatinine, bicarbonate; (c) urinalysis—protein, glucose, pH, Ketones, nitrates, blood (d.) pregnancy test.

Screening/Baseline Visit—Informed consent for study participation signed. Complete history (including record of systemic and topical medication, both prescription and non-prescription). Physical exam—Comprehensive skin exam and photography of the treatment area and hair count. (e) Review criteria for inclusion/exclusion and determine eligibility.

Daily Clinic Visits for treatment—waxing of the treatment area (for first 30 days only) followed by topical application of Treatment. Blood and urine samples for Hematology, Serum chemistry, Urine analysis, Isporopranol serum/urine level and siRNA detection in serum/urine will be obtained monthly. Photography of the treatment area and hair count will be performed weekly. Subjects will be interviewed for subjective side effects weekly.

Monthly Clinic Visits for follow-up—Blood and urine samples for Hematology, Serum chemistry, Urine analysis, Isporopranol serum/urine level and siRNA detection in serum/urine will be obtained. Photography of the treatment area and hair count. Subjects will be interviewed for subjective side effects.

Study Site—Subjects will be seen at the clinical facilities for the study.

Study Drugs

siRNAs for the study are are oligonucleotides with RNAi activity that is specific to mRNA sequences present in the human hairless mRNA. This study will utilize a mixture of 8-10 different siRNAs. To date there is no data available of topical cutaneous application of any deoxy-ribozymes. The siRNAs to be used in this study will be provided by a manufacturer offering custom synthesized human grade oligonucleotides.

Study Questionnaires

All subjects will complete study questionnaires at baseline.

Study Subjects

Criteria—Inclusion—(i) Study subjects must be 18 to 35 years of age, female of Hispanic ethnicity. (ii) Have no previous medical history of hair growth abnormalities or endocrine, renal, autoimmune, cardiac, pulmonary, hematological or psychiatric disorders. (iii) Other inclusion criteria: (iv) The subject has provided written informed consent prior to administration of any study-related procedures. (v) The subject has been using adequate contraception since her last menses and will use adequate contraception during the study, is not lactating, and has a documented negative serum pregnancy test within 14 days prior to the first dose of study medication. (vi) The subject is willing to abstain from any voluntary alteration of body hair of the treated area. (vii) The subject is willing to abstain from application of prescription and over the counter topical medications for the duration of the study, including moisturizers, emollients and sunscreens. (viii) The subject is willing to return for scheduled follow-up visits for the duration of the study. (ix) The subject must meet the following laboratory criteria during a time not to exceed 8 weeks prior to randomization: 1) hemoglobin level of greater than 12.0 (women) or 13.0 (men); 2) WBC count greater than 3000/mm³; 3) platelet count greater than 125,000; 4) BUN within normal limits; 5) electrolytes within normal limits; 6) creatinine≦1.5×ULN; 7) AST≦1.5×ULN; 8) ALT≦1.5×ULN; 9) total bilirubin within normal limits; and 10) creatinin clearance within normal limits.

Exclusion—(i) existence of any medical conditions listed above. (ii) any laboratory values that do not meet the criteria listed above. (iii) Pregnancy or lactation. (iv) Invasive cancer or anticipated hormonal, chemo-, or radiotherapy while participating in the study. (v) Any medical or psychosocial condition that, in the opinion of the investigator, could jeopardize subject's participation in this study.

Recruitment of Subjects

Potential subjects for this Study will be recruited from among residents in proximity to the study site because of the daily visit requirements. Subjects with Hispanic ethnicity will be recruited to avoid inter-ethnicity variations of hair density and follicle site as well as blonde hair that is less appropriate for complete hair count and photography.

EXAMPLE 3

Hair Removal Using In Vivo Knockdown of Hairless mRNA

It was demonstrated that inhibiting the expression of hairless mRNA in an animal model system created essentially a hairless condition. This exemplary test was conducted using ribozymes targeting the hairless mRNA, and is described in Cserhalmi-Friedman et al., Exp Dermatol., 2004 March; 13(3):155-62, which is incorporated herein by reference in its entirety.

Short Term Results in Newborn Mice

The mice, who were gender-matched littermates, were sacrificed after four weeks of treatment that started immediately after the animals were born. All treated mice demonstrated a variable degree of visible sparseness of hair at the treated area of the back, which was not observed in the control animals treated with nonspecific deoxyribozymes. The specimens taken from the control animal show the presence of large number of hair follicles in anagen V stage, corresponding to the clinical appearance. In contrast, the samples taken from the treated mice demonstrate the presence of smaller hair follicles with morphological features similar to those observed in anagen III stage (i.e.: hair shaft did not reach the level of the sebaceous gland). A large portion of the hair follicles in the treated region showed delayed anagen development as well as significant dilatation of the hair canal, reminiscent of utricles characteristic of the hairless phenotype. In these samples, we observed several large cysts filled with keratinous material and remnants of coiled and degraded hair follicles. These dermal cysts are believed to be the result of hair follicle disintegration and abnormal hair shaft formation. Importantly, dermal cysts are hallmark features of the hairless phenotype and usually contain either keratinous mass or a degraded hair shaft, as seen in the sample taken from the skin of a hairless mouse. The inhibition of hair growth, formation of the utriculi, and appearance of dermal cysts were present in all treated mice, but were not detected in any control animals.

b. Long Term Results in Newborn Mice

Another group of littermates of identical gender was sacrificed after seven weeks of treatment that started immediately after the animals were born. A noticeable decrease in the density of hair was present in the treated animals as compared to the control mice treated with on specific deoxyribozymes. The sample from the control animals showed the presence of regularly spaced telogen hair follicles. In the treated area, we observed a significantly decreased number of follicles with large areas of the skin devoid of any hair follicles at all. In the treated area, we detected the presence of large cysts filled with amorphous keratin material, corresponding to dermal cysts, which are characteristics of the hairless phenotype. Histopathology of the treated area showed the presence of small dense groups of cells with condensed nuclei in the deep dermis. These cell groups were reminiscent of detached dermal papillae, which are typically found in hairless mice. The lack of hair follicles, the presence of dermal cysts and the detached dermal papillae were present in every treated animal, while all the control animals showed the presence of evenly spaced telogen follicles.

c. Results in Depilated Animals

This group of eight week old female littermates was wax-depilated and subsequently sacrificed after four weeks of treatment that began immediately after the depilation. Clinically, the control animals showed active hair regrowth in the depilated area.

In contrast, the hair regrowth was of lesser magnitude in the treated mice, and the hair became sparse (not shown). Histopathology of the control mouse skin shows the presence of a large number of hair follicles in advanced anagen. In the samples taken from the treated animals, the treated regions could be easily identified by the lack of depilation-induced hair regrowth. These untreated hair follicles were identical to those observed in the control animals treated with nonspecific deoxyribozymes. On histology, the treated area with small telogen hair follicles could be easily distinguished from neighboring untreated area with hair follicles at advanced anagen stages, suggesting that in the treated portion of skin the hair follicles were not able to enter depilation-induced anagen at all, or exhibited much lower growth rates compare to control skin.

All patents and other references cited in the specification are indicative of the level of skill of those skilled in the art to which the invention pertains, and are incorporated by reference in their entireties, including any tables and figures, to the same extent as if each reference had been incorporated by reference in its entirety individually.

One skilled in the art would readily appreciate that the present invention is well adapted to obtain the ends and advantages mentioned, as well as those inherent therein. The methods, variances, and compositions described herein as presently representative of preferred embodiments are exemplary and are not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art, which are encompassed within the spirit of the invention, are defined by the scope of the claims.

It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. For example, variations can be made to the number, length, and chemical modifications in the dsRNA. Thus, such additional embodiments are within the scope of the present invention and the following claims.

The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms “comprising”, “consisting essentially of” and “consisting of” may be replaced with either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.

In addition, where features or aspects of the invention are described in terms of Markush groups or other grouping of alternatives, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group or other group.

Also, unless indicated to the contrary, where various numerical values are provided for embodiments, additional embodiments are described by taking any 2 different values as the endpoints of a range. Such ranges are also within the scope of the described invention.

Thus, additional embodiments are within the scope of the invention and within the following claims.

TABLE 1
cDNA Human Hairless 19-mer Target Sequences and
Complement Referenced to NM_005144-
Homo sapiens hairless homolog (mouse) (HR),
transcript variant 1, complete mRNA (1-5699 bp).
(SEQ ID NO: for Sense equals (2X − 1) SEQ ID
NO: for Antisense equals (2X), (e.g. where
X = 1 Sense has SEQ ID NO: 1 and Antisense
has SEQ ID NO: 2)
X	Sense (5′-3′)	Antisense (5′-3′)
1	TCTCCCGGGAGCCACTCCC	GGGAGTGGCTCCCGGGAGA
2	CTCCCGGGAGCCACTCCCA	TGGGAGTGGCTCCCGGGAG
3	TCCCGGGAGCCACTCCCAT	ATGGGAGTGGCTCCCGGGA
4	CCCGGGAGCCACTCCCATG	CATGGGAGTGGCTCCCGGG
5	CCGGGAGCCACTCCCATGG	CCATGGGAGTGGCTCCCGG
6	CGGGAGCCACTCCCATGGG	CCCATGGGAGTGGCTCCCG
7	GGGAGCCACTCCCATGGGC	GCCCATGGGAGTGGCTCCC
8	GGAGCCACTCCCATGGGCG	CGCCCATGGGAGTGGCTCC
9	GAGCCACTCCCATGGGCGC	GCGCCCATGGGAGTGGCTC
10	AGCCACTCCCATGGGCGCC	GGCGCCCATGGGAGTGGCT
11	GCCACTCCCATGGGCGCCT	AGGCGCCCATGGGAGTGGC
12	CCACTCCCATGGGCGCCTC	GAGGCGCCCATGGGAGTGG
13	CACTCCCATGGGCGCCTCT	AGAGGCGCCCATGGGAGTG
14	ACTCCCATGGGCGCCTCTC	GAGAGGCGCCCATGGGAGT
15	CTCCCATGGGCGCCTCTCC	GGAGAGGCGCCCATGGGAG
16	TCCCATGGGCGCCTCTCCA	TGGAGAGGCGCCCATGGGA
17	CCCATGGGCGCCTCTCCAG	CTGGAGAGGCGCCCATGGG
18	CCATGGGCGCCTCTCCAGC	GCTGGAGAGGCGCCCATGG
19	CATGGGCGCCTCTCCAGCC	GGCTGGAGAGGCGCCCATG
20	ATGGGCGCCTCTCCAGCCC	GGGCTGGAGAGGCGCCGAT
21	TGGGCGCCTCTCCAGCCCC	GGGGCTGGAGAGGCGCCCA
22	GGGCGCCTCTCCAGCCCCT	AGGGGCTGGAGAGGCGCCC
23	GGCGCCTCTCCAGCCCCTG	CAGGGGCTGGAGAGGCGCC
24	GCGCCTCTCCAGCCCCTGG	CCAGGGGCTGGAGAGGCGC
25	CGCCTCTCCAGCCCCTGGC	GCCAGGGGCTGGAGAGGCG
26	GCCTCTCCAGCCCCTGGCC	GGCCAGGGGCTGGAGAGGC
27	CCTCTCCAGCCCCTGGCCT	AGGCCAGGGGCTGGAGAGG
28	CTCTCCAGCCCCTGGCCTG	CAGGCCAGGGGCTGGAGAG
29	TCTCCAGCCCCTGGCCTGG	CCAGGCCAGGGGCTGGAGA
30	CTCCAGCCCCTGGCCTGGA	TCCAGGCCAGGGGCTGGAG
31	TCCAGCCCCTGGCCTGGAA	TTCCAGGCCAGGGGCTGGA
32	CCAGCCCCTGGCCTGGAAG	CTTCCAGGCCAGGGGCTGG
33	CAGCCCCTGGCCTGGAAGC	GCTTCCAGGCCAGGGGCTG
34	AGCCCCTGGCCTGGAAGCA	TGCTTCCAGGCCAGGGGCT
35	GCCCCTGGCCTGGAAGCAC	GTGCTTCCAGGCCAGGGGC
36	CCCCTGGCCTGGAAGCACC	GGTGCTTCCAGGCCAGGGG
37	CCCTGGCCTGGAAGCACCA	TGGTGCTTCCAGGCCAGGG
38	CCTGGCCTGGAAGCACCAG	CTGGTGCTTCCAGGCCAGG
39	CTGGCCTGGAAGCACCAGG	CCTGGTGCTTCCAGGCCAG
40	TGGCCTGGAAGCACCAGGA	TCCTGGTGCTTCCAGGCCA
41	GGCCTGGAAGCACCAGGAA	TTCCTGGTGCTTCCAGGCC
42	GCCTGGAAGCACCAGGAAC	GTTCCTGGTGCTTCCAGGC
43	CCTGGAAGCACCAGGAACC	GGTTCCTGGTGCTTCCAGG
44	CTGGAAGCACCAGGAACCC	GGGTTCCTGGTGCTTCCAG
45	TGGAAGCACCAGGAACCCT	AGGGTTCCTGGTGCTTCCA
46	GGAAGCACCAGGAACCCTG	CAGGGTTCCTGGTGCTTCC
47	GAAGCACCAGGAACCCTGG	CCAGGGTTCCTGGTGCTTC
48	AAGCACCAGGAACCCTGGG	CCCAGGGTTCCTGGTGCTT
49	AGCACCAGGAACCCTGGGG	CCCCAGGGTTCCTGGTGCT
50	GCACCAGGAACCCTGGGGA	TCCCCAGGGTTCCTGGTGC
51	CACCAGGAACCCTGGGGAT	ATCCCCAGGGTTCCTGGTG
52	ACCAGGAACCCTGGGGATG	CATCCCCAGGGTTCCTGGT
53	CCAGGAACCCTGGGGATGG	CCATCCCCAGGGTTCCTGG
54	CAGGAACCCTGGGGATGGG	CCCATCCCCAGGGTTCCTG
55	AGGAACCCTGGGGATGGGG	CCCCATCCCCAGGGTTCCT
56	GGAACCCTGGGGATGGGGC	GCCCCATCCCCAGGGTTCC
57	GAACCCTGGGGATGGGGCA	TGCCCCATCCCCAGGGTTC
58	AACCCTGGGGATGGGGCAG	CTGCCCCATCCCCAGGGTT
59	ACCCTGGGGATGGGGCAGA	TCTGCCCCATCCCCAGGGT
60	CCCTGGGGATGGGGCAGAC	GTCTGCCCCATCCCCAGGG
61	CCTGGGGATGGGGCAGACC	GGTCTGCCCCATCCCCAGG
62	CTGGGGATGGGGCAGACCC	GGGTCTGCCCCATCCCCAG
63	TGGGGATGGGGCAGACCCT	AGGGTCTGCCCCATCCCCA
64	GGGGATGGGGCAGACCCTC	GAGGGTCTGCCCCATCCCC
65	GGGATGGGGCAGACCCTCA	TGAGGGTCTGCCCCATCCC
66	GGATGGGGCAGACCCTCAC	GTGAGGGTCTGCCCCATCC
67	GATGGGGCAGACCCTCACA	TGTGAGGGTCTGCCCCATC
68	ATGGGGCAGACCCTCACAG	CTGTGAGGGTCTGCCCCAT
69	TGGGGCAGACCCTCACAGC	GCTGTGAGGGTCTGCCCCA
70	GGGGCAGACCCTCACAGCC	GGCTGTGAGGGTCTGCCCC
71	GGGCAGACCCTCACAGCCC	GGGCTGTGAGGGTCTGCCC
72	GGCAGACCCTCACAGCCCG	CGGGCTGTGAGGGTCTGCC
73	GCAGACCCTCACAGCCCGG	CCGGGCTGTGAGGGTCTGC
74	CAGACCCTCACAGCCCGGG	CCCGGGCTGTGAGGGTCTG
75	AGACCCTCACAGCCCGGGG	CCCCGGGCTGTGAGGGTCT
76	GACCCTCACAGCCCGGGGT	ACCCCGGGCTGTGAGGGTC
77	ACCCTCACAGCCCGGGGTC	GACCCCGGGCTGTGAGGGT
78	CCCTCACAGCCCGGGGTCT	AGACCCCGGGCTGTGAGGG
79	CCTCACAGCCCGGGGTCTG	CAGACCCCGGGCTGTGAGG
80	CTCACAGCCCGGGGTCTGG	CCAGACCCCGGGCTGTGAG
81	TCACAGCCCGGGGTCTGGA	TCCAGACCCCGGGCTGTGA
82	CACAGCCCGGGGTCTGGAG	CTCCAGACCCCGGGCTGTG
83	ACAGCCCGGGGTCTGGAGC	GCTCCAGACCCCGGGCTGT
84	CAGCCCGGGGTCTGGAGCC	GGCTCCAGACCCCGGGCTG
85	AGCCCGGGGTCTGGAGCCG	CGGCTCCAGACCCCGGGCT
86	GCCCGGGGTCTGGAGCCGG	CCGGCTCCAGACCCCGGGC
87	CCCGGGGTCTGGAGCCGGT	ACCGGCTCCAGACCCCGGG
88	CCGGGGTCTGGAGCCGGTG	CACCGGCTCCAGACCCCGG
89	CGGGGTCTGGAGCCGGTGT	ACACCGGCTCCAGACCCCG
90	GGGGTCTGGAGCCGGTGTC	GACACCGGCTCCAGACCCC
91	GGGTCTGGAGCCGGTGTCG	CGACACCGGCTCCAGACCC
92	GGTCTGGAGCCGGTGTCGG	CCGACACCGGCTCCAGACC
93	GTCTGGAGCCGGTGTCGGA	TCCGACACCGGCTCCAGAC
94	TCTGGAGCCGGTGTCGGAG	CTCCGACACCGGCTCCAGA
95	CTGGAGCCGGTGTCGGAGC	GCTCCGACACCGGCTCCAG
96	TGGAGCCGGTGTCGGAGCT	AGCTCCGACACCGGCTCCA
97	GGAGCCGGTGTCGGAGCTC	GAGCTCCGACACCGGCTCC
98	GAGCCGGTGTCGGAGCTCA	TGAGCTCCGACACCGGCTC
99	AGCCGGTGTCGGAGCTCAT	ATGAGCTCCGACACCGGCT
100	GCCGGTGTCGGAGCTCATC	GATGAGCTCCGACACCGGC
101	CCGGTGTCGGAGCTCATCT	AGATGAGCTCCGACACCGG
102	CGGTGTCGGAGCTCATCTG	CAGATGAGCTCCGACACCG
103	GGTGTCGGAGCTCATCTGG	CCAGATGAGCTCCGACACC
104	GTGTCGGAGCTCATCTGGG	CCCAGATGAGCTCCGACAC
105	TGTCGGAGCTCATCTGGGC	GCCCAGATGAGCTCCGACA
106	GTCGGAGCTCATCTGGGCC	GGCCCAGATGAGCTCCGAC
107	TCGGAGCTCATCTGGGCCC	GGGCCCAGATGAGCTCCGA
108	CGGAGCTCATCTGGGCCCA	TGGGCCCAGATGAGCTCCG
109	GGAGCTCATCTGGGCCCAT	ATGGGCCCAGATGAGCTCC
110	GAGCTCATCTGGGCCCATG	CATGGGCCCAGATGAGCTC
111	AGCTCATCTGGGCCCATGA	TCATGGGCCCAGATGAGCT
112	GCTCATCTGGGCCCATGAC	GTCATGGGCCCAGATGAGC
113	CTCATCTGGGCCCATGACC	GGTCATGGGCCCAGATGAG
114	TCATCTGGGCCCATGACCT	AGGTCATGGGCCCAGATGA
115	CATCTGGGCCCATGACCTC	GAGGTCATGGGCCCAGATG
116	ATCTGGGCCCATGACCTCT	AGAGGTCATGGGCCCAGAT
117	TCTGGGCCCATGACCTCTC	GAGAGGTCATGGGCCCAGA
118	CTGGGCCCATGACCTCTCC	GGAGAGGTCATGGGCCCAG
119	TGGGCCCATGACCTCTCCA	TGGAGAGGTCATGGGCCCA
120	GGGCCCATGACCTCTCCAG	CTGGAGAGGTCATGGGCCC
121	GGCCCATGACCTCTCCAGA	TCTGGAGAGGTCATGGGCC
122	GCCCATGACCTCTCCAGAC	GTCTGGAGAGGTCATGGGC
123	CCCATGACCTCTCCAGACA	TGTCTGGAGAGGTCATGGG
124	CCATGACCTCTCCAGACAT	ATGTCTGGAGAGGTCATGG
125	CATGACCTCTCCAGACATT	AATGTCTGGAGAGGTCATG
126	ATGACCTCTCCAGACATTT	AAATGTCTGGAGAGGTCAT
127	TGACCTCTCCAGACATTTG	CAAATGTCTGGAGAGGTCA
128	GACCTCTCCAGACATTTGG	CCAAATGTCTGGAGAGGTC
129	ACCTCTCCAGACATTTGGC	GCCAAATGTCTGGAGAGGT
130	CCTCTCCAGACATTTGGCA	TGCCAAATGTCTGGAGAGG
131	CTCTCCAGACATTTGGCAA	TTGCCAAATGTCTGGAGAG
132	TCTCCAGACATTTGGCAAA	TTTGCCAAATGTCTGGAGA
133	CTCCAGACATTTGGCAAAA	TTTTGCCAAATGTCTGGAG
134	TCCAGACATTTGGCAAAAT	ATTTTGCCAAATGTCTGGA
135	CCAGACATTTGGCAAAATC	GATTTTGCCAAATGTCTGG
136	CAGACATTTGGCAAAATCA	TGATTTTGCCAAATGTCTG
137	AGACATTTGGCAAAATCAA	TTGATTTTGCCAAATGTCT
138	GACATTTGGCAAAATCAAG	CTTGATTTTGCCAAATGTC
139	ACATTTGGCAAAATCAAGG	CCTTGATTTTGCCAAATGT
140	CATTTGGCAAAATCAAGGC	GCCTTGATTTTGCCAAATG
141	ATTTGGCAAAATCAAGGCC	GGCCTTGATTTTGCCAAAT
142	TTTGGCAAAATCAAGGCCC	GGGCCTTGATTTTGCCAAA
143	TTGGCAAAATCAAGGCCCT	AGGGCCTTGATTTTGCCAA
144	TGGCAAAATCAAGGCCCTT	AAGGGCCTTGATTTTGCCA
145	GGCAAAATCAAGGCCCTTA	TAAGGGCCTTGATTTTGCC
146	GCAAAATCAAGGCCCTTAG	CTAAGGGCCTTGATTTTGC
147	CAAAATCAAGGCCCTTAGA	TCTAAGGGCCTTGATTTTG
148	AAAATCAAGGCCCTTAGAC	GTCTAAGGGCCTTGATTTT
149	AAATCAAGGCCCTTAGACC	GGTCTAAGGGCCTTGATTT
150	AATCAAGGCCCTTAGACCA	TGGTCTAAGGGCCTTGATT
151	ATCAAGGCCCTTAGACCAG	CTGGTCTAAGGGCCTTGAT
152	TCAAGGCCCTTAGACCAGG	CCTGGTCTAAGGGCCTTGA
153	CAAGGCCCTTAGACCAGGG	CCCTGGTCTAAGGGCCTTG
154	AAGGCCCTTAGACCAGGGA	TCCCTGGTCTAAGGGCCTT
155	AGGCCCTTAGACCAGGGAC	GTCCCTGGTCTAAGGGCCT
156	GGCCCTTAGACCAGGGACA	TGTCCCTGGTCTAAGGGCC
157	GCCCTTAGACCAGGGACAG	CTGTCCCTGGTCTAAGGGC
158	CCCTTAGACCAGGGACAGA	TCTGTCCCTGGTCTAAGGG
159	CCTTAGACCAGGGACAGAC	GTCTGTCCCTGGTCTAAGG
160	CTTAGACCAGGGACAGACC	GGTCTGTCCCTGGTCTAAG
161	TTAGACCAGGGACAGACCC	GGGTCTGTCCCTGGTCTAA
162	TAGACCAGGGACAGACCCA	TGGGTCTGTCCCTGGTCTA
163	AGACCAGGGACAGACCCAA	TTGGGTCTGTCCCTGGTCT
164	GACCAGGGACAGACCCAAG	CTTGGGTCTGTCCCTGGTC
165	ACCAGGGACAGACCCAAGC	GCTTGGGTCTGTCCCTGGT
166	CCAGGGACAGACCCAAGCC	GGCTTGGGTCTGTCCCTGG
167	CAGGGACAGACCCAAGCCC	GGGCTTGGGTCTGTCCCTG
168	AGGGACAGACCCAAGCCCA	TGGGCTTGGGTCTGTCCCT
169	GGGACAGACCCAAGCCCAG	CTGGGCTTGGGTCTGTCCC
170	GGACAGACCCAAGCCCAGG	CCTGGGCTTGGGTCTGTCC
171	GACAGACCCAAGCCCAGGC	GCCTGGGCTTGGGTCTGTC
172	ACAGACCCAAGCCCAGGCC	GGCCTGGGCTTGGGTCTGT
173	CAGACCCAAGCCCAGGCCC	GGGCCTGGGCTTGGGTCTG
174	AGACCCAAGCCCAGGCCCT	AGGGCCTGGGCTTGGGTCT
175	GACCCAAGCCCAGGCCCTC	GAGGGCCTGGGCTTGGGTC
176	ACCCAAGCCCAGGCCCTCC	GGAGGGCCTGGGCTTGGGT
177	CCCAAGCCCAGGCCCTCCC	GGGAGGGCCTGGGCTTGGG
178	CCAAGCCCAGGCCCTCCCA	TGGGAGGGCCTGGGCTTGG
179	CAAGCCCAGGCCCTCCCAG	CTGGGAGGGCCTGGGCTTG
180	AAGCCCAGGCCCTCCCAGA	TCTGGGAGGGCCTGGGCTT
181	AGCCCAGGCCCTCCCAGAG	CTCTGGGAGGGCCTGGGCT
182	GCCCAGGCCCTCCCAGAGG	CCTCTGGGAGGGCCTGGGC
183	CCCAGGCCCTCCCAGAGGT	ACCTCTGGGAGGGCCTGGG
184	CCAGGCCCTCCCAGAGGTC	GACCTCTGGGAGGGCCTGG
185	CAGGCCCTCCCAGAGGTCC	GGACCTCTGGGAGGGCCTG
186	AGGCCCTCCCAGAGGTCCT	AGGACCTCTGGGAGGGCCT
187	GGCCCTCCCAGAGGTCCTA	TAGGACCTCTGGGAGGGCC
188	GCCCTCCCAGAGGTCCTAG	CTAGGACCTCTGGGAGGGC
189	CCCTCCCAGAGGTCCTAGG	CCTAGGACCTCTGGGAGGG
190	CCTCCCAGAGGTCCTAGGA	TCCTAGGACCTCTGGGAGG
191	CTCCCAGAGGTCCTAGGAC	GTCCTAGGACCTCTGGGAG
192	TCCCAGAGGTCCTAGGACG	CGTCCTAGGACCTCTGGGA
193	CCCAGAGGTCCTAGGACGC	GCGTCCTAGGACCTCTGGG
194	CCAGAGGTCCTAGGACGCA	TGCGTCCTAGGACCTCTGG
195	CAGAGGTCCTAGGACGCAA	TTGCGTCCTAGGACCTCTG
196	AGAGGTCCTAGGACGCAAC	GTTGCGTCCTAGGACCTCT
197	GAGGTCCTAGGACGCAACC	GGTTGCGTCCTAGGACCTC
198	AGGTCCTAGGACGCAACCC	GGGTTGCGTCCTAGGACCT
199	GGTCCTAGGACGCAACCCT	AGGGTTGCGTCCTAGGACC
200	GTCCTAGGACGCAACCCTT	AAGGGTTGCGTCCTAGGAC
201	TCCTAGGACGCAACCCTTT	AAAGGGTTGCGTCCTAGGA
202	CCTAGGACGCAACCCTTTG	CAAAGGGTTGCGTCCTAGG
203	CTAGGACGCAACCCTTTGT	ACAAAGGGTTGCGTCCTAG
204	TAGGACGCAACCCTTTGTG	CACAAAGGGTTGCGTCCTA
205	AGGACGCAACCCTTTGTGC	GCACAAAGGGTTGCGTCCT
206	GGACGCAACCCTTTGTGCC	GGCACAAAGGGTTGCGTCC
207	GACGCAACCCTTTGTGCCC	GGGCACAAAGGGTTGCGTC
208	ACGCAACCCTTTGTGCCCT	AGGGCACAAAGGGTTGCGT
209	CGCAACCCTTTGTGCCCTT	AAGGGCACAAAGGGTTGCG
210	GCAACCCTTTGTGCCCTTG	CAAGGGCACAAAGGGTTGC
211	CAACCCTTTGTGCCCTTGG	CCAAGGGCACAAAGGGTTG
212	AACCCTTTGTGCCCTTGGG	CCCAAGGGCACAAAGGGTT
213	ACCCTTTGTGCCCTTGGGC	GCCCAAGGGCACAAAGGGT
214	CCCTTTGTGCCCTTGGGCT	AGCCCAAGGGCACAAAGGG
215	CCTTTGTGCCCTTGGGCTC	GAGCCCAAGGGCACAAAGG
216	CTTTGTGCCCTTGGGCTCT	AGAGCCCAAGGGCACAAAG
217	TTTGTGCCCTTGGGCTCTG	CAGAGCCCAAGGGCACAAA
218	TTGTGCCCTTGGGCTCTGG	CCAGAGCCCAAGGGCACAA
219	TGTGCCCTTGGGCTCTGGA	TCCAGAGCCCAAGGGCACA
220	GTGCCCTTGGGCTCTGGAA	TTCCAGAGCCCAAGGGCAC
221	TGCCCTTGGGCTCTGGAAG	CTTCCAGAGCCCAAGGGCA
222	GCCCTTGGGCTCTGGAAGA	TCTTCCAGAGCCCAAGGGC
223	CCCTTGGGCTCTGGAAGAG	CTCTTCCAGAGCCCAAGGG
224	CCTTGGGCTCTGGAAGAGG	CCTCTTCCAGAGCCCAAGG
225	CTTGGGCTCTGGAAGAGGT	ACCTCTTCCAGAGCCCAAG
226	TTGGGCTCTGGAAGAGGTT	AACCTCTTCCAGAGCCCAA
227	TGGGCTCTGGAAGAGGTTT	AAACCTCTTCCAGAGCCCA
228	GGGCTCTGGAAGAGGTTTG	CAAACCTCTTCCAGAGCCC
229	GGCTCTGGAAGAGGTTTGG	CCAAACCTCTTCCAGAGCC
230	GCTCTGGAAGAGGTTTGGG	CCCAAACCTCTTCCAGAGC
231	CTCTGGAAGAGGTTTGGGA	TCCCAAACCTCTTCCAGAG
232	TCTGGAAGAGGTTTGGGAA	TTCCCAAACCTCTTCCAGA
233	CTGGAAGAGGTTTGGGAAG	CTTCCCAAACCTCTTCCAG
234	TGGAAGAGGTTTGGGAAGG	CCTTCCCAAACCTCTTCCA
235	GGAAGAGGTTTGGGAAGGG	CCCTTCCCAAACCTCTTCC
236	GAAGAGGTTTGGGAAGGGT	ACCCTTCCCAAACCTCTTC
237	AAGAGGTTTGGGAAGGGTT	AACCCTTCCCAAACCTCTT
238	AGAGGTTTGGGAAGGGTTT	AAACCCTTCCCAAACCTCT
239	GAGGTTTGGGAAGGGTTTG	CAAACCCTTCCCAAACCTC
240	AGGTTTGGGAAGGGTTTGG	CCAAACCCTTCCCAAACCT
241	GGTTTGGGAAGGGTTTGGG	CCCAAACCCTTCCCAAACC
242	GTTTGGGAAGGGTTTGGGG	CCCCAAACCCTTCCCAAAC
243	TTTGGGAAGGGTTTGGGGT	ACCCCAAACCCTTCCCAAA
244	TTGGGAAGGGTTTGGGGTG	CACCCCAAACCCTTCCCAA
245	TGGGAAGGGTTTGGGGTGG	CCACCCCAAACCCTTCCCA
246	GGGAAGGGTTTGGGGTGGA	TCCACCCCAAACCCTTCCC
247	GGAAGGGTTTGGGGTGGAA	TTCCACCCCAAACCCTTCC
248	GAAGGGTTTGGGGTGGAAG	CTTCCACCCCAAACCCTTC
249	AAGGGTTTGGGGTGGAAGA	TCTTCCACCCCAAACCCTT
250	AGGGTTTGGGGTGGAAGAT	ATCTTCCACCCCAAACCCT
251	GGGTTTGGGGTGGAAGATG	CATCTTCCACCCCAAACCC
252	GGTTTGGGGTGGAAGATGG	CCATCTTCCACCCCAAACC
253	GTTTGGGGTGGAAGATGGC	GCCATCTTCCACCCCAAAC
254	TTTGGGGTGGAAGATGGCA	TGCCATCTTCCACCCCAAA
255	TTGGGGTGGAAGATGGCAA	TTGCCATCTTCCACCCCAA
256	TGGGGTGGAAGATGGCAAA	TTTGCCATCTTCCACCCCA
257	GGGGTGGAAGATGGCAAAG	CTTTGCCATCTTCCACCCC
258	GGGTGGAAGATGGCAAAGA	TCTTTGCCATCTTCCACCC
259	GGTGGAAGATGGCAAAGAG	CCTCTTTGCCATCTTCCACC
260	GTGGAAGATGGCAAAGAGC	GCTCTTTGCCATCTTCCAC
261	TGGAAGATGGCAAAGAGCA	TGCTCTTTGCCATCTTCCA
262	GGAAGATGGCAAAGAGCAG	CTGCTCTTTGCCATCTTCC
263	GAAGATGGCAAAGAGCAGC	GCTGCTCTTTGCCATCTTC
264	AAGATGGCAAAGAGCAGCT	AGCTGCTCTTTGCCATCTT
265	AGATGGCAAAGAGCAGCTT	AAGCTGCTCTTTGCCATCT
266	GATGGCAAAGAGCAGCTTG	CAAGCTGCTCTTTGCCATC
267	ATGGCAAAGAGCAGCTTGG	CCAAGCTGCTCTTTGCCAT
268	TGGCAAAGAGCAGCTTGGC	GCCAAGCTGCTCTTTGCCA
269	GGCAAAGAGCAGCTTGGCC	GGCCAAGCTGCTCTTTGCC
270	GCAAAGAGCAGCTTGGCCA	TGGCCAAGCTGCTCTTTGC
271	CAAAGAGCAGCTTGGCCAG	CTGGCCAAGCTGCTCTTTG
272	AAAGAGCAGCTTGGCCAGG	CCTGGCCAAGCTGCTCTTT
273	AAGAGCAGCTTGGCCAGGT	ACCTGGCCAAGCTGCTCTT
274	AGAGCAGCTTGGCCAGGTG	CACCTGGCCAAGCTGCTCT
275	GAGCAGCTTGGCCAGGTGA	TCACCTGGCCAAGCTGCTC
276	AGCAGCTTGGCCAGGTGAG	CTCACCTGGCCAAGCTGCT
277	GCAGCTTGGCCAGGTGAGG	CCTCACCTGGCCAAGCTGC
278	CAGCTTGGCCAGGTGAGGA	TCCTCACCTGGCCAAGCTG
279	AGCTTGGCCAGGTGAGGAT	ATCCTCACCTGGCCAAGCT
280	GCTTGGCCAGGTGAGGATG	CATCCTCACCTGGCCAAGC
281	CTTGGCCAGGTGAGGATGA	TCATCCTCACCTGGCCAAG
282	TTGGCCAGGTGAGGATGAG	CTCATCCTCACCTGGCCAA
283	TGGCCAGGTGAGGATGAGG	CCTCATCCTCACCTGGCCA
284	GGCCAGGTGAGGATGAGGC	GCCTCATCCTCACCTGGCC
285	GCCAGGTGAGGATGAGGCA	TGCCTCATCCTCACCTGGC
286	CCAGGTGAGGATGAGGCAG	CTGCCTCATCCTCACCTGG
287	CAGGTGAGGATGAGGCAGG	CCTGCCTCATCCTCACCTG
288	AGGTGAGGATGAGGCAGGG	CCCTGCCTCATCCTCACCT
289	GGTGAGGATGAGGCAGGGC	GCCCTGCCTCATCCTCACC
290	GTGAGGATGAGGCAGGGCA	TGCCCTGCCTCATCCTCAC
291	TGAGGATGAGGCAGGGCAG	CTGCCCTGCCTCATCCTCA
292	GAGGATGAGGCAGGGCAGA	TCTGCCCTGCCTCATCCTC
293	AGGATGAGGCAGGGCAGAC	GTCTGCCCTGCCTCATCCT
294	GGATGAGGCAGGGCAGACA	TGTCTGCCCTGCCTCATCC
295	GATGAGGCAGGGCAGACAC	GTGTCTGCCCTGCCTCATC
296	ATGAGGCAGGGCAGACACA	TGTGTCTGCCCTGCCTCAT
297	TGAGGCAGGGCAGACACAG	CTGTGTCTGCCCTGCCTCA
298	GAGGCAGGGCAGACACAGG	CCTGTGTCTGCCCTGCCTC
299	AGGCAGGGCAGACACAGGC	GCCTGTGTCTGCCCTGCCT
300	GGCAGGGCAGACACAGGCC	GGCCTGTGTCTGCCCTGCC
301	GCAGGGCAGACACAGGCCA	TGGCCTGTGTCTGCCCTGC
302	CAGGGCAGACACAGGCCAG	CTGGCCTGTGTCTGCCCTG
303	AGGGCAGACACAGGCCAGT	ACTGGCCTGTGTCTGCCCT
304	GGGCAGACACAGGCCAGTG	CACTGGCCTGTGTCTGCCC
305	GGCAGACAGAGGCCAGTGG	CCACTGGCCTGTGTCTGCC
306	GCAGACACAGGCCAGTGGG	CCCACTGGCCTGTGTCTGC
307	CAGACACAGGCCAGTGGGG	CCCCACTGGCCTGTGTCTG
308	AGACACAGGCCAGTGGGGC	GCCCCACTGGCCTGTGTCT
309	GACACAGGCCAGTGGGGCG	CGCCCCACTGGCCTGTGTC
310	ACACAGGCCAGTGGGGCGT	ACGCCCCACTGGCCTGTGT
311	CACAGGCCAGTGGGGCGTG	CACGCCCCACTGGCCTGTG
312	ACAGGCCAGTGGGGCGTGC	GCACGCCCCACTGGCCTGT
313	CAGGCCAGTGGGGCGTGCC	GGCACGCCCCACTGGCCTG
314	AGGCCAGTGGGGCGTGCCA	TGGCACGCCCCACTGGCCT
315	GGCCAGTGGGGCGTGCCAT	ATGGCACGCCCCACTGGCC
316	GCCAGTGGGGCGTGCCATG	CATGGCACGCCCCACTGGC
317	CCAGTGGGGCGTGCCATGT	ACATGGCACGCCCCACTGG
318	CAGTGGGGCGTGCCATGTG	CACATGGCACGCCCCACTG
319	AGTGGGGCGTGCCATGTGC	GCACATGGCACGCCCCACT
320	GTGGGGCGTGCCATGTGCC	GGCACATGGCACGCCCCAC
321	TGGGGCGTGCCATGTGCCA	TGGCACATGGCACGCCCCA
322	GGGGCGTGCCATGTGCCAC	GTGGCACATGGCACGCCCC
323	GGGCGTGCCATGTGCCACA	TGTGGCACATGGCACGCCC
324	GGCGTGCCATGTGCCACAG	CTGTGGCACATGGCACGCC
325	GCGTGCCATGTGCCACAGA	TCTGTGGCACATGGCACGC
326	CGTGCCATGTGCCACAGAT	ATCTGTGGCACATGGCACG
327	GTGCCATGTGCCACAGATG	CATCTGTGGCACATGGCAC
328	TGCCATGTGCCACAGATGG	CCATCTGTGGCACATGGCA
329	GCCATGTGCCACAGATGGA	TCCATCTGTGGCACATGGC
330	CCATGTGCCACAGATGGAG	CTCCATCTGTGGCACATGG
331	CATGTGCCACAGATGGAGA	TCTCCATCTGTGGCACATG
332	ATGTGCCACAGATGGAGAG	CTCTCCATCTGTGGCACAT
333	TGTGCCACAGATGGAGAGG	CCTCTCCATCTGTGGCACA
334	GTGCCACAGATGGAGAGGA	TCCTCTCCATCTGTGGCAC
335	TGCCACAGATGGAGAGGAC	GTCCTCTCCATCTGTGGCA
336	GCCACAGATGGAGAGGACC	GGTCCTCTCCATCTGTGGC
337	CCACAGATGGAGAGGACCA	TGGTCCTCTCCATCTGTGG
338	CACAGATGGAGAGGACCAG	CTGGTCCTCTCCATCTGTG
339	ACAGATGGAGAGGACCAGG	CCTGGTCCTCTCCATCTGT
340	CAGATGGAGAGGACCAGGA	TCCTGGTCCTCTCCATCTG
341	AGATGGAGAGGACCAGGAG	CTCCTGGTCCTCTCCATCT
342	GATGGAGAGGACCAGGAGC	GCTCCTGGTCCTCTCCATC
343	ATGGAGAGGACCAGGAGCC	GGCTCCTGGTCCTCTCCAT
344	TGGAGAGGACCAGGAGCCA	TGGCTCCTGGTCCTCTCCA
345	GGAGAGGACCAGGAGCCAG	CTGGCTCCTGGTCCTCTCC
346	GAGAGGACCAGGAGCCAGT	ACTGGCTCCTGGTCCTCTC
347	AGAGGACCAGGAGCCAGTG	CACTGGCTCCTGGTCCTCT
348	GAGGACCAGGAGCCAGTGG	CCACTGGCTCCTGGTCCTC
349	AGGACCAGGAGCCAGTGGC	GCCACTGGCTCCTGGTCCT
350	GGACCAGGAGCCAGTGGCC	GGCCACTGGCTCCTGGTCC
351	GACCAGGAGCCAGTGGCCC	GGGCCACTGGCTCCTGGTC
352	ACCAGGAGCCAGTGGCCCG	CGGGCCACTGGCTCCTGGT
353	CCAGGAGCCAGTGGCCCGG	CCGGGCCACTGGCTCCTGG
354	CAGGAGCCAGTGGCCCGGC	GCCGGGCCACTGGCTCCTG
355	AGGAGCCAGTGGCCCGGCA	TGCCGGGCCACTGGCTCCT
356	GGAGCCAGTGGCCCGGCAG	CTGCCGGGCCACTGGCTCC
357	GAGCCAGTGGCCCGGCAGG	CCTGCCGGGCCACTGGCTC
358	AGCCAGTGGCCCGGCAGGC	GCCTGCCGGGCCACTGGCT
359	GCCAGTGGCCCGGCAGGCA	TGCCTGCCGGGCCACTGGC
360	CCAGTGGCCCGGCAGGCAC	GTGCCTGCCGGGCCACTGG
361	CAGTGGCCCGGCAGGCACA	TGTGCCTGCCGGGCCACTG
362	AGTGGCCCGGCAGGCACAG	CTGTGCCTGCCGGGCCACT
363	GTGGCCCGGCAGGCACAGC	GCTGTGCCTGCCGGGCCAC
364	TGGCCCGGCAGGCACAGCC	GGCTGTGCCTGCCGGGCCA
365	GGCCCGGCAGGCACAGCCC	GGGCTGTGCCTGCCGGGCC
366	GCCCGGCAGGCACAGCCCG	CGGGCTGTGCCTGCCGGGC
367	CCCGGCAGGCACAGCCCGG	CCGGGCTGTGCCTGCCGGG
368	CCGGCAGGCACAGCCCGGT	ACCGGGCTGTGCCTGCCGG
369	CGGCAGGCACAGCCCGGTT	AACCGGGCTGTGCCTGCCG
370	GGCAGGCACAGCCCGGTTG	CAACCGGGCTGTGCCTGCC
371	GCAGGCACAGCCCGGTTGG	CCAACCGGGCTGTGCCTGC
372	CAGGCACAGCCCGGTTGGC	GCCAACCGGGCTGTGCCTG
373	AGGCACAGCCCGGTTGGCG	CGCCAACCGGGCTGTGCCT
374	GGCACAGCCCGGTTGGCGT	ACGCCAACCGGGCTGTGCC
375	GCACAGCCCGGTTGGCGTG	CACGCCAACCGGGCTGTGC
376	CACAGCCCGGTTGGCGTGG	CCACGCCAACCGGGCTGTG
377	ACAGCCCGGTTGGCGTGGG	CCCACGCCAACCGGGCTGT
378	CAGCCCGGTTGGCGTGGGC	GCCCACGCCAACCGGGCTG
379	AGCCCGGTTGGCGTGGGCC	GGCCCACGCCAACCGGGCT
380	GCCCGGTTGGCGTGGGCCA	TGGCCCACGCCAACCGGGC
381	CCCGGTTGGCGTGGGCCAG	CTGGCCCACGCCAACCGGG
382	CCGGTTGGCGTGGGCCAGA	TCTGGCCCACGCCAACCGG
383	CGGTTGGCGTGGGCCAGAG	CTCTGGCCCACGCCAACCG
384	GGTTGGCGTGGGCCAGAGC	GCTCTGGCCCACGCCAACC
385	GTTGGCGTGGGCCAGAGCG	CGCTCTGGCCCACGCCAAC
386	TTGGCGTGGGCCAGAGCGC	GCGCTCTGGCCCACGCCAA
387	TGGCGTGGGCCAGAGCGCC	GGCGCTCTGGCCCACGCCA
388	GGCGTGGGCCAGAGCGCCC	GGGCGCTCTGGCCCACGCC
389	GCGTGGGCCAGAGCGCCCA	TGGGCGCTCTGGCCCACGC
390	CGTGGGCCAGAGCGCCCAT	ATGGGCGCTCTGGCCCACG
391	GTGGGCCAGAGCGCCCATC	GATGGGCGCTCTGGCCCAC
392	TGGGCCAGAGCGCCCATCA	TGATGGGCGCTCTGGCCCA
393	GGGCCAGAGCGCCCATCAC	GTGATGGGCGCTCTGGCCC
394	GGCCAGAGCGCCCATCACT	AGTGATGGGCGCTCTGGCC
395	GCCAGAGCGCCCATCACTG	CAGTGATGGGCGCTCTGGC
396	CCAGAGCGCCCATCACTGA	TCAGTGATGGGCGCTCTGG
397	CAGAGCGCCCATCACTGAC	GTCAGTGATGGGCGCTCTG
398	AGAGCGCCCATCACTGACC	GGTCAGTGATGGGCGCTCT
399	GAGCGCCCATCACTGACCC	GGGTCAGTGATGGGCGCTC
400	AGCGCCCATCACTGACCCG	CGGGTCAGTGATGGGCGCT
401	GCGCCCATCACTGACCCGT	ACGGGTCAGTGATGGGCGC
402	CGCCCATCACTGACCCGTG	CACGGGTCAGTGATGGGCG
403	GCCCATCACTGACCCGTGA	TCACGGGTCAGTGATGGGC
404	CCCATCACTGACCCGTGAG	CTCACGGGTCAGTGATGGG
405	CCATCACTGACCCGTGAGA	TCTCACGGGTCAGTGATGG
406	CATCACTGACCCGTGAGAA	TTCTCACGGGTCAGTGATG
407	ATCACTGACCCGTGAGAAC	GTTCTCACGGGTCAGTGAT
408	TCACTGACCCGTGAGAACT	AGTTCTCACGGGTCAGTGA
409	CACTGACCCGTGAGAACTC	GAGTTCTCACGGGTCAGTG
410	ACTGACCCGTGAGAACTCG	CGAGTTCTCACGGGTCAGT
411	CTGACCCGTGAGAACTCGA	TCGAGTTCTCACGGGTCAG
412	TGACCCGTGAGAACTCGAC	GTCGAGTTCTCACGGGTCA
413	GACCCGTGAGAACTCGACT	AGTCGAGTTCTCACGGGTC
414	ACCCGTGAGAACTCGACTG	CAGTCGAGTTCTCACGGGT
415	CCCGTGAGAACTCGACTGC	GCAGTCGAGTTCTCACGGG
416	CCGTGAGAACTCGACTGCC	GGCAGTCGAGTTCTCACGG
417	CGTGAGAACTCGACTGCCC	GGGCAGTCGAGTTCTCACG
418	GTGAGAACTCGACTGCCCC	GGGGCAGTCGAGTTCTCAC
419	TGAGAACTCGACTGCCCCT	AGGGGCAGTCGAGTTCTCA
420	GAGAACTCGACTGCCCCTG	CAGGGGCAGTCGAGTTCTC
421	AGAACTCGACTGCCCCTGC	GCAGGGGCAGTCGAGTTCT
422	GAACTCGACTGCCCCTGCC	GGCAGGGGCAGTCGAGTTC
423	AACTCGACTGCCCCTGCCA	TGGCAGGGGCAGTCGAGTT
424	ACTCGACTGCCCCTGCCAG	CTGGCAGGGGCAGTCGAGT
425	CTCGACTGCCCCTGCCAGC	GCTGGCAGGGGCAGTCGAG
426	TCGACTGCCCCTGCCAGCT	AGCTGGCAGGGGCAGTCGA
427	CGACTGCCCCTGCCAGCTC	GAGCTGGCAGGGGCAGTCG
428	GACTGCCCCTGCCAGCTCT	AGAGCTGGCAGGGGCAGTC
429	ACTGCCCCTGCCAGCTCTG	CAGAGCTGGCAGGGGCAGT
430	CTGCCCCTGCCAGCTCTGG	CCAGAGCTGGCAGGGGCAG
431	TGCCCCTGCCAGCTCTGGC	GCCAGAGCTGGCAGGGGCA
432	GCCCCTGCCAGCTCTGGCA	TGCCAGAGCTGGCAGGGGC
433	CCCCTGCCAGCTCTGGCAC	GTGCCAGAGCTGGCAGGGG
434	CCCTGCCAGCTCTGGCACT	AGTGCCAGAGCTGGCAGGG
435	CCTGCCAGCTCTGGCACTG	CAGTGCCAGAGCTGGCAGG
436	CTGCCAGCTCTGGCACTGC	GCAGTGCCAGAGCTGGCAG
437	TGCCAGCTCTGGCACTGCC	GGCAGTGCCAGAGCTGGCA
438	GCCAGCTCTGGCACTGCCC	GGGCAGTGCCAGAGCTGGC
439	CCAGCTCTGGCACTGCCCC	GGGGCAGTGCCAGAGCTGG
440	CAGCTCTGGCACTGCCCCC	GGGGGCAGTGCCAGAGCTG
441	AGCTCTGGCACTGCCCCCT	AGGGGGCAGTGCCAGAGCT
442	GCTCTGGCACTGCCCCCTC	GAGGGGGCAGTGCCAGAGC
443	CTCTGGCACTGCCCCCTCC	GGAGGGGGCAGTGCCAGAG
444	TCTGGCACTGCCCCCTCCC	GGGAGGGGGCAGTGCCAGA
445	CTGGCACTGCCCCCTCCCA	TGGGAGGGGGCAGTGCCAG
446	TGGCACTGCCCCCTCCCAG	CTGGGAGGGGGCAGTGCCA
447	GGCACTGCCCCCTCCCAGC	GCTGGGAGGGGGCAGTGCC
448	GCACTGCCCCCTCCCAGCC	GGCTGGGAGGGGGCAGTGC
449	CACTGCCCCCTCCCAGCCG	CGGCTGGGAGGGGGCAGTG
450	ACTGCCCCCTCCCAGCCGC	GCGGCTGGGAGGGGGCAGT
451	CTGCCCCCTCCCAGCCGCC	GGCGGCTGGGAGGGGGCAG
452	TGCCCCCTCCCAGCCGCCC	GGGCGGCTGGGAGGGGGCA
453	GCCCCCTCCCAGCCGCCCC	GGGGCGGCTGGGAGGGGGC
454	CCCCCTCCCAGCCGCCCCG	CGGGGCGGCTGGGAGGGGG
455	CCCCTCCCAGCCGCCCCGC	GCGGGGCGGCTGGGAGGGG
456	CCCTCCCAGCCGCCCCGCC	GGCGGGGCGGCTGGGAGGG
457	CCTCCCAGCCGCCCCGCCC	GGGCGGGGCGGCTGGGAGG
458	CTCCCAGCCGCCCCGCCCT	AGGGCGGGGCGGCTGGGAG
459	TCCCAGCCGCCCCGCCCTA	TAGGGCGGGGCGGCTGGGA
460	CCCAGCCGCCCCGCCCTAG	CTAGGGCGGGGCGGCTGGG
461	CCAGCCGCCCCGCCCTAGC	GCTAGGGCGGGGCGGCTGG
462	CAGCCGCCCCGCCCTAGCA	TGCTAGGGCGGGGCGGCTG
463	AGCCGCCCCGCCCTAGCAC	GTGCTAGGGCGGGGCGGCT
464	GCCGCCCCGCCCTAGCACC	GGTGCTAGGGCGGGGCGGC
465	CCGCCCCGCCCTAGCACCC	GGGTGCTAGGGCGGGGCGG
466	CGCCCCGCCCTAGCACCCT	AGGGTGCTAGGGCGGGGCG
467	GCCCCGCCCTAGCACCCTG	CAGGGTGCTAGGGCGGGGC
468	CCCCGCCCTAGCACCCTGG	CCAGGGTGCTAGGGCGGGG
469	CCCGCCCTAGCACCCTGGG	CCCAGGGTGCTAGGGCGGG
470	CCGCCCTAGCACCCTGGGG	CCCCAGGGTGCTAGGGCGG
471	CGCCCTAGCACCCTGGGGG	CCCCCAGGGTGCTAGGGCG
472	GCCCTAGCACCCTGGGGGG	CCCCCCAGGGTGCTAGGGC
473	CCCTAGCACCCTGGGGGGC	GCCCCCCAGGGTGCTAGGG
474	CCTAGCACCCTGGGGGGCA	TGCCCCCCAGGGTGCTAGG
475	CTAGCACCCTGGGGGGCAC	GTGCCCCCCAGGGTGCTAG
476	TAGCACCCTGGGGGGCACC	GGTGCCCCCCAGGGTGCTA
477	AGCACCCTGGGGGGCACCC	GGGTGCCCCCCAGGGTGCT
478	GCACCCTGGGGGGCACCCC	GGGGTGCCCCCCAGGGTGC
479	CACCCTGGGGGGCACCCCG	CGGGGTGCCCCCCAGGGTG
480	ACCCTGGGGGGCACCCCGC	GCGGGGTGCCCCCCAGGGT
481	CCCTGGGGGGCACCCCGCC	GGCGGGGTGCCCCCCAGGG
482	CCTGGGGGGCACCCCGCCC	GGGCGGGGTGCCCCCCAGG
483	CTGGGGGGCACCCCGCCCA	TGGGCGGGGTGCCCCCCAG
484	TGGGGGGCACCCCGCCCAA	TTGGGCGGGGTGCCCCCCA
485	GGGGGGCACCCCGCCCAAC	GTTGGGCGGGGTGCCCCCC
486	GGGGGCACCCCGCCCAACC	GGTTGGGCGGGGTGCCCCC
487	GGGGCACCCCGCCCAACCG	CGGTTGGGCGGGGTGCCCC
488	GGGCACCCCGCCCAACCGT	ACGGTTGGGCGGGGTGCCC
489	GGCACCCCGCCCAACCGTG	CACGGTTGGGCGGGGTGCC
490	GCACCCCGCCCAACCGTGG	CCACGGTTGGGCGGGGTGC
491	CACCCCGCCCAACCGTGGC	GCCACGGTTGGGCGGGGTG
492	ACCCCGCCCAACCGTGGCC	GGCCACGGTTGGGCGGGGT
493	CCCCGCCCAACCGTGGCCT	AGGCCACGGTTGGGCGGGG
494	CCCGCCCAACCGTGGCCTG	CAGGCCACGGTTGGGCGGG
495	CCGCCCAACCGTGGCCTGG	CCAGGCCACGGTTGGGCGG
496	CGCCCAACCGTGGCCTGGT	ACCAGGCCACGGTTGGGCG
497	GCCCAACCGTGGCCTGGTC	GACCAGGCCACGGTTGGGC
498	CCCAACCGTGGCCTGGTCC	GGACCAGGCCACGGTTGGG
499	CCAACCGTGGCCTGGTCCG	CGGACCAGGCCACGGTTGG
500	CAACCGTGGCCTGGTCCGG	CCGGACCAGGCCACGGTTG
501	AACCGTGGCCTGGTCCGGC	GCCGGACCAGGCCACGGTT
502	ACCGTGGCCTGGTCCGGCC	GGCCGGACCAGGCCACGGT
503	CCGTGGCCTGGTCCGGCCC	GGGCCGGACCAGGCCACGG
504	CGTGGCCTGGTCCGGCCCC	GGGGCCGGACCAGGCCACG
505	GTGGCCTGGTCCGGCCCCT	AGGGGCCGGACCAGGCCAC
506	TGGCCTGGTCCGGCCCCTC	GAGGGGCCGGACCAGGCCA
507	GGCCTGGTCCGGCCCCTCC	GGAGGGGCCGGACCAGGCC
508	GCCTGGTCCGGCCCCTCCC	GGGAGGGGCCGGACCAGGC
509	CCTGGTCCGGCCCCTCCCG	CGGGAGGGGCCGGACCAGG
510	CTGGTCCGGCCCCTCCCGC	GCGGGAGGGGCCGGACCAG
511	TGGTCCGGCCCCTCCCGCC	GGCGGGAGGGGCCGGACCA
512	GGTCCGGCCCCTCCCGCCC	GGGCGGGAGGGGCCGGACC
513	GTCCGGCCCCTCCCGCCCT	AGGGCGGGAGGGGCCGGAC
514	TCCGGCCCCTCCCGCCCTT	AAGGGCGGGAGGGGCCGGA
515	CCGGCCCCTCCCGCCCTTT	AAAGGGCGGGAGGGGCCGG
516	CGGCCCCTCCCGCCCTTTG	CAAAGGGCGGGAGGGGCCG
517	GGCCCCTCCCGCCCTTTGC	GCAAAGGGCGGGAGGGGCC
518	GCCCCTCCCGCCCTTTGCT	AGCAAAGGGCGGGAGGGGC
519	CCCCTCCCGCCCTTTGCTC	GAGCAAAGGGCGGGAGGGG
520	CCCTCCCGCCCTTTGCTCC	GGAGCAAAGGGCGGGAGGG
521	CCTCCCGCCCTTTGCTCCA	TGGAGCAAAGGGCGGGAGG
522	CTCCCGCCCTTTGCTCCAG	CTGGAGCAAAGGGCGGGAG
523	TCCCGCCCTTTGCTCCAGT	ACTGGAGCAAAGGGCGGGA
524	CCCGCCCTTTGCTCCAGTT	AACTGGAGCAAAGGGCGGG
525	CCGCCCTTTGCTCCAGTTC	GAACTGGAGCAAAGGGCGG
526	CGCCCTTTGCTCCAGTTCC	GGAACTGGAGCAAAGGGCG
527	GCCCTTTGCTCCAGTTCCC	GGGAACTGGAGCAAAGGGC
528	CCCTTTGCTCCAGTTCCCG	CGGGAACTGGAGCAAAGGG
529	CCTTTGCTCCAGTTCCCGG	CCGGGAACTGGAGCAAAGG
530	CTTTGCTCCAGTTCCCGGG	CCCGGGAACTGGAGCAAAG
531	TTTGCTCCAGTTCCCGGGC	GCCCGGGAACTGGAGCAAA
532	TTGCTCCAGTTCCCGGGCT	AGCCCGGGAACTGGAGCAA
533	TGCTCCAGTTCCCGGGCTT	AAGCCCGGGAACTGGAGCA
534	GCTCCAGTTCCCGGGCTTG	CAAGCCCGGGAACTGGAGC
535	CTCCAGTTCCCGGGCTTGG	CCAAGCCCGGGAACTGGAG
536	TCCAGTTCCCGGGCTTGGC	GCCAAGCCCGGGAACTGGA
537	CCAGTTCCCGGGCTTGGCA	TGCCAAGCCCGGGAACTGG
538	CAGTTCCCGGGCTTGGCAC	GTGCCAAGCCCGGGAACTG
539	AGTTCCCGGGCTTGGCACC	GGTGCCAAGCCCGGGAACT
540	GTTCCCGGGCTTGGCACCT	AGGTGCCAAGCCCGGGAAC
541	TTCCCGGGCTTGGCACCTA	TAGGTGCCAAGCCCGGGAA
542	TCCCGGGCTTGGCACCTAT	ATAGGTGCCAAGCCCGGGA
543	CCCGGGCTTGGCACCTATA	TATAGGTGCCAAGCCCGGG
544	CCGGGCTTGGCACCTATAG	CTATAGGTGCCAAGCCCGG
545	CGGGCTTGGCACCTATAGT	ACTATAGGTGCCAAGCCCG
546	GGGCTTGGCACCTATAGTG	CACTATAGGTGCCAAGCCC
547	GGCTTGGCACCTATAGTGG	CCACTATAGGTGCCAAGCC
548	GCTTGGCACCTATAGTGGG	CCCACTATAGGTGCCAAGC
549	CTTGGCACCTATAGTGGGG	CCCCACTATAGGTGCCAAG
550	TTGGCACCTATAGTGGGGG	CCCCCACTATAGGTGCCAA
551	TGGCACCTATAGTGGGGGT	ACCCCCACTATAGGTGCCA
552	GGCACCTATAGTGGGGGTG	CACCCCCACTATAGGTGCC
553	GCACCTATAGTGGGGGTGC	GCACCCCCACTATAGGTGC
554	CACCTATAGTGGGGGTGCC	GGCACCCCCACTATAGGTG
555	ACCTATAGTGGGGGTGCCG	CGGCACCCCCACTATAGGT
556	CCTATAGTGGGGGTGCCGC	GCGGCACCCCCACTATAGG
557	CTATAGTGGGGGTGCCGCC	GGCGGCACCCCCACTATAG
558	TATAGTGGGGGTGCCGCCC	GGGCGGCACCCCCACTATA
559	ATAGTGGGGGTGCCGCCCG	CGGGCGGCACCCCCACTAT
560	TAGTGGGGGTGCCGCCCGC	GCGGGCGGCACCCCCACTA
561	AGTGGGGGTGCCGCCCGCC	GGCGGGCGGCACCCCCACT
562	GTGGGGGTGCCGCCCGCCT	AGGCGGGCGGCACCCCCAC
563	TGGGGGTGCCGCCCGCCTG	CAGGCGGGCGGCACCCCCA
564	GGGGGTGCCGCCCGCCTGC	GCAGGCGGGCGGCACCCCC
565	GGGGTGCCGCCCGCCTGCC	GGCAGGCGGGCGGCACCCC
566	GGGTGCCGCCCGCCTGCCA	TGGCAGGCGGGCGGCACCC
567	GGTGCCGCCCGCCTGCCAG	CTGGCAGGCGGGCGGCACC
568	GTGCCGCCCGCCTGCCAGG	CCTGGCAGGCGGGCGGCAC
569	TGCCGCCCGCCTGCCAGGC	GCCTGGCAGGCGGGCGGCA
570	GCCGCCCGCCTGCCAGGCT	AGCCTGGCAGGCGGGCGGC
571	CCGCCCGCCTGCCAGGCTC	GAGCCTGGCAGGCGGGCGG
572	CGCCCGCCTGCCAGGCTCC	GGAGCCTGGCAGGCGGGCG
573	GCCCGCCTGCCAGGCTCCG	CGGAGCCTGGCAGGCGGGC
574	CCCGCCTGCCAGGCTCCGG	CCGGAGCCTGGCAGGCGGG
575	CCGCCTGCCAGGCTCCGGG	CCCGGAGCCTGGCAGGCGG
576	CGCCTGCCAGGCTCCGGGG	CCCCGGAGCCTGGCAGGCG
577	GCCTGCCAGGCTCCGGGGC	GCCCCGGAGCCTGGCAGGC
578	CCTGCCAGGCTCCGGGGCC	GGCCCCGGAGCCTGGCAGG
579	CTGCCAGGCTCCGGGGCCG	CGGCCCCGGAGCCTGGCAG
580	TGCCAGGCTCCGGGGCCGG	CCGGCCCCGGAGCCTGGCA
581	GCCAGGCTCCGGGGCCGGG	CCCGGCCCCGGAGCCTGGC
582	CCAGGCTCCGGGGCCGGGC	GCCCGGCCCCGGAGCCTGG
583	CAGGCTCCGGGGCCGGGCC	GGCCCGGCCCCGGAGCCTG
584	AGGCTCCGGGGCCGGGCCC	GGGCCCGGCCCCGGAGCCT
585	GGCTCCGGGGCCGGGCCCA	TGGGCCCGGCCCCGGAGCC
586	GCTCCGGGGCCGGGCCCAC	GTGGGCCCGGCCCCGGAGC
587	CTCCGGGGCCGGGCCCACG	CGTGGGCCCGGCCCCGGAG
588	TCCGGGGCCGGGCCCACGG	CCGTGGGCCCGGCCCCGGA
589	CCGGGGCCGGGCCCACGGG	CCCGTGGGCCCGGCCCCGG
590	CGGGGCCGGGCCCACGGGA	TCCCGTGGGCCCGGCCCCG
591	GGGGCCGGGCCCACGGGAG	CTCCCGTGGGCCCGGCCCC
592	GGGCCGGGCCCACGGGAGG	CCTCCCGTGGGCCCGGCCC
593	GGCCGGGCCCACGGGAGGG	CCCTCCCGTGGGCCCGGCC
594	GCCGGGCCCACGGGAGGGT	ACCCTCCCGTGGGCCCGGC
595	CCGGGCCCACGGGAGGGTG	CACCCTCCCGTGGGCCCGG
596	CGGGCCCACGGGAGGGTGG	CCACCCTCCCGTGGGCCCG
597	GGGCCCACGGGAGGGTGGG	CCCACCCTCCCGTGGGCCC
598	GGCCCACGGGAGGGTGGGG	CCCCACCCTCCCGTGGGCC
599	GCCCACGGGAGGGTGGGGC	GCCCCACCCTCCCGTGGGC
600	CCCACGGGAGGGTGGGGCG	CGCCCCACCCTCCCGTGGG
601	CCACGGGAGGGTGGGGCGG	CCGCCCCACCCTCCCGTGG
602	CACGGGAGGGTGGGGCGGC	GCCGCCCCACCCTCCCGTG
603	ACGGGAGGGTGGGGCGGCT	AGCCGCCCCACCCTCCCGT
604	CGGGAGGGTGGGGCGGCTG	CAGCCGCCCCACCCTCCCG
605	GGGAGGGTGGGGCGGCTGG	CCAGCCGCCCCACCCTCCC
606	GGAGGGTGGGGCGGCTGGG	CCCAGCCGCCCCACCCTCC
607	GAGGGTGGGGCGGCTGGGA	TCCCAGCCGCCCCACCCTC
608	AGGGTGGGGCGGCTGGGAA	TTCCCAGCCGCCCCACCCT
609	GGGTGGGGCGGCTGGGAAG	CTTCCCAGCCGCCCCACCC
610	GGTGGGGCGGCTGGGAAGC	GCTTCCCAGCCGCCCCACC
611	GTGGGGCGGCTGGGAAGCT	AGCTTCCCAGCCGCCCCAC
612	TGGGGCGGCTGGGAAGCTG	CAGCTTCCCAGCCGCCCCA
613	GGGGCGGCTGGGAAGCTGG	CCAGCTTCCCAGCCGCCCC
614	GGGCGGCTGGGAAGCTGGC	GCCAGCTTCCCAGCCGCCC
615	GGCGGCTGGGAAGCTGGCA	TGCCAGCTTCCCAGCCGCC
616	GCGGCTGGGAAGCTGGCAC	GTGCCAGCTTCCCAGCCGC
617	CGGCTGGGAAGCTGGCACG	CGTGCCAGCTTCCCAGCCG
618	GGCTGGGAAGCTGGCACGC	GCGTGCCAGCTTCCCAGCC
619	GCTGGGAAGCTGGCACGCT	AGCGTGCCAGCTTCCCAGC
620	CTGGGAAGCTGGCACGCTG	CAGCGTGCCAGCTTCCCAG
621	TGGGAAGCTGGCACGCTGC	GCAGCGTGCCAGCTTCCCA
622	GGGAAGCTGGCACGCTGCC	GGCAGCGTGCCAGCTTCCC
623	GGAAGCTGGCACGCTGCCC	GGGCAGCGTGCCAGCTTCC
624	GAAGCTGGCACGCTGCCCC	GGGGCAGCGTGCCAGCTTC
625	AAGCTGGCACGCTGCCCCG	CGGGGCAGCGTGCCAGCTT
626	AGCTGGCACGCTGCCCCGG	CCGGGGCAGCGTGCCAGCT
627	GCTGGCACGCTGCCCCGGG	CCCGGGGCAGCGTGCCAGC
628	CTGGCACGCTGCCCCGGGG	CCCCGGGGCAGCGTGCCAG
629	TGGCACGCTGCCCCGGGGG	CCCCCGGGGCAGCGTGCCA
630	GGCACGCTGCCCCGGGGGA	TCCCCCGGGGCAGCGTGCC
631	GCACGCTGCCCCGGGGGAG	CTCCCCCGGGGCAGCGTGC
632	CACGCTGCCCCGGGGGAGC	GCTCCCCCGGGGCAGCGTG
633	ACGCTGCCCCGGGGGAGCC	GGCTCCCCCGGGGCAGCGT
634	CGCTGCCCCGGGGGAGCCT	AGGCTCCCCCGGGGCAGCG
635	GCTGCCCCGGGGGAGCCTC	GAGGCTCCCCCGGGGCAGC
636	CTGCCCCGGGGGAGCCTCT	AGAGGCTCCCCCGGGGCAG
637	TGCCCCGGGGGAGCCTCTC	GAGAGGCTCCCCCGGGGCA
638	GCCCCGGGGGAGCCTCTCT	AGAGAGGCTCCCCCGGGGC
639	CCCCGGGGGAGCCTCTCTC	GAGAGAGGCTCCCCCGGGG
640	CCCGGGGGAGCCTCTCTCG	CGAGAGAGGCTCCCCCGGG
641	CCGGGGGAGCCTCTCTCGG	CCGAGAGAGGCTCCCCCGG
642	CGGGGGAGCCTCTCTCGGC	GCCGAGAGAGGCTCCCCCG
643	GGGGGAGCCTCTCTCGGCA	TGCCGAGAGAGGCTCCCCC
644	GGGGAGCCTCTCTCGGCAG	CTGCCGAGAGAGGCTCCCC
645	GGGAGCCTCTCTCGGCAGG	CCTGCCGAGAGAGGCTCCC
646	GGAGCCTCTCTCGGCAGGC	GCCTGCCGAGAGAGGCTCC
647	GAGCCTCTCTCGGCAGGCG	CGCCTGCCGAGAGAGGCTC
648	AGCCTCTCTCGGCAGGCGC	GCGCCTGCCGAGAGAGGCT
649	GCCTCTCTCGGCAGGCGCC	GGCGCCTGCCGAGAGAGGC
650	CCTCTCTCGGCAGGCGCCC	GGGCGCCTGCCGAGAGAGG
651	CTCTCTCGGCAGGCGCCCG	CGGGCGCCTGCCGAGAGAG
652	TCTCTCGGCAGGCGCCCGG	CCGGGCGCCTGCCGAGAGA
653	CTCTCGGCAGGCGCCCGGG	CCCGGGCGCCTGCCGAGAG
654	TCTCGGCAGGCGCCCGGGT	ACCCGGGCGCCTGCCGAGA
655	CTCGGCAGGCGCCCGGGTG	CACCCGGGCGCCTGCCGAG
656	TCGGCAGGCGCCCGGGTGC	GCACCCGGGCGCCTGCCGA
657	CGGCAGGCGCCCGGGTGCC	GGCACCCGGGCGCCTGCCG
658	GGCAGGCGCCCGGGTGCCG	CGGCACCCGGGCGCCTGCC
659	GCAGGCGCCCGGGTGCCGC	GCGGCACCCGGGCGCCTGC
660	CAGGCGCCCGGGTGCCGCG	CGCGGCACCCGGGCGCCTG
661	AGGCGCCCGGGTGCCGCGG	CCGCGGCACCCGGGCGCCT
662	GGCGCCCGGGTGCCGCGGG	CCCGCGGCACCCGGGCGCC
663	GCGCCCGGGTGCCGCGGGG	CCCCGCGGCACCCGGGCGC
664	CGCCCGGGTGCCGCGGGGG	CCCCCGCGGCACCCGGGCG
665	GCCCGGGTGCCGCGGGGGG	CCCCCCGCGGCACCCGGGC
666	CCCGGGTGCCGCGGGGGGG	CCCCCCCGCGGCACCCGGG
667	CCGGGTGCCGCGGGGGGGA	TCCCCCCCGCGGCACCCGG
668	CGGGTGCCGCGGGGGGGAG	CTCCCCCCCGCGGCACCCG
669	GGGTGCCGCGGGGGGGAGG	CCTCCCCCCCGCGGCACCC
670	GGTGCCGCGGGGGGGAGGG	CCCTCCCCCCCGCGGCACC
671	GTGCCGCGGGGGGGAGGGG	CCCCTCCCCCCCGCGGCAC
672	TGCCGCGGGGGGGAGGGGG	CCCCCTCCCCCCCGCGGCA
673	GCCGCGGGGGGGAGGGGGA	TCCCCCTCCCCCCCGCGGC
674	CCGCGGGGGGGAGGGGGAA	TTCCCCCTCCCCCCCGCGG
675	CGCGGGGGGGAGGGGGAAC	GTTCCCCCTCCCCCCCGCG
676	GCGGGGGGGAGGGGGAACA	TGTTCCCCCTCCCCCCCGC
677	CGGGGGGGAGGGGGAACAA	TTGTTCCCCCTCCCCCCCG
678	GGGGGGGAGGGGGAACAAA	TTTGTTCCCCCTCCCCCCC
679	GGGGGGAGGGGGAACAAAG	CTTTGTTCCCCCTCCCCCC
680	GGGGGAGGGGGAACAAAGG	CCTTTGTTCCCCCTCCCCC
681	GGGGAGGGGGAACAAAGGG	CCCTTTGTTCCCCCTCCCC
682	GGGAGGGGGAACAAAGGGC	GCCCTTTGTTCCCCCTCCC
683	GGAGGGGGAACAAAGGGCT	AGCCCTTTGTTCCCCCTCC
684	GAGGGGGAACAAAGGGCTC	GAGCCCTTTGTTCCCCCTC
685	AGGGGGAACAAAGGGCTCA	TGAGCCCTTTGTTCCCCCT
686	GGGGGAACAAAGGGCTCAT	ATGAGCCCTTTGTTCCCCC
687	GGGGAACAAAGGGCTCATT	AATGAGCCCTTTGTTCCCC
688	GGGAACAAAGGGCTCATTC	GAATGAGCCCTTTGTTCCC
689	GGAACAAAGGGCTCATTCT	AGAATGAGCCCTTTGTTCC
690	GAACAAAGGGCTCATTCTC	GAGAATGAGCCCTTTGTTC
691	AACAAAGGGCTCATTCTCC	GGAGAATGAGCCCTTTGTT
692	ACAAAGGGCTCATTCTCCC	GGGAGAATGAGCCCTTTGT
693	CAAAGGGCTCATTCTCCCC	GGGGAGAATGAGCCCTTTG
694	AAAGGGCTCATTCTCCCCG	CGGGGAGAATGAGCCCTTT
695	AAGGGCTCATTCTCCCCGT	ACGGGGAGAATGAGCCCTT
696	AGGGCTCATTCTCCCCGTG	CACGGGGAGAATGAGCCCT
697	GGGCTCATTCTCCCCGTGC	GCACGGGGAGAATGAGCCC
698	GGCTCATTCTCCCCGTGCG	CGCACGGGGAGAATGAGCC
699	GCTCATTCTCCCCGTGCGC	GCGCACGGGGAGAATGAGC
700	CTCATTCTCCCCGTGCGCA	TGCGCACGGGGAGAATGAG
701	TCATTCTCCCCGTGCGCAG	CTGCGCACGGGGAGAATGA
702	CATTCTCCCCGTGCGCAGC	GCTGCGCACGGGGAGAATG
703	ATTCTCCCCGTGCGCAGCC	GGCTGCGCACGGGGAGAAT
704	TTCTCCCCGTGCGCAGCCG	CGGCTGCGCACGGGGAGAA
705	TCTCCCCGTGCGCAGCCGG	CCGGCTGCGCACGGGGAGA
706	CTCCCCGTGCGCAGCCGGT	ACCGGCTGCGCACGGGGAG
707	TCCCCGTGCGCAGCCGGTG	CACCGGCTGCGCACGGGGA
708	CCCCGTGCGCAGCCGGTGG	CCACCGGCTGCGCACGGGG
709	CCCGTGCGCAGCCGGTGGC	GCCACCGGCTGCGCACGGG
710	CCGTGCGCAGCCGGTGGCA	TGCCACCGGCTGCGCACGG
711	CGTGCGCAGCCGGTGGCAT	ATGCCACCGGCTGCGCACG
712	GTGCGCAGCCGGTGGCATC	GATGCCACCGGCTGCGCAC
713	TGCGCAGCCGGTGGCATCG	CGATGCCACCGGCTGCGCA
714	GCGCAGCCGGTGGCATCGC	GCGATGCCACCGGCTGCGC
715	CGCAGCCGGTGGCATCGCC	GGCGATGCCACCGGCTGCG
716	GCAGCCGGTGGCATCGCCG	CGGCGATGCCACCGGCTGC
717	CAGCCGGTGGCATCGCCGG	CCGGCGATGCCACCGGCTG
718	AGCCGGTGGCATCGCCGGG	CCCGGCGATGCCACCGGCT
719	GCCGGTGGCATCGCCGGGG	CCCCGGCGATGCCACCGGC
720	CCGGTGGCATCGCCGGGGC	GCCCCGGCGATGCCACCGG
721	CGGTGGCATCGCCGGGGCG	CGCCCCGGCGATGCCACCG
722	GGTGGCATCGCCGGGGCGT	ACGCCCCGGCGATGCCACC
723	GTGGCATCGCCGGGGCGTT	AACGCCCCGGCGATGCCAC
724	TGGCATCGCCGGGGCGTTG	CAACGCCCCGGCGATGCCA
725	GGCATCGCCGGGGCGTTGG	CCAACGCCCCGGCGATGCC
726	GCATCGCCGGGGCGTTGGC	GCCAACGCCCCGGCGATGC
727	CATCGCCGGGGCGTTGGCG	CGCCAACGCCCCGGCGATG
728	ATCGCCGGGGCGTTGGCGG	CCGCCAACGCCCCGGCGAT
729	TCGCCGGGGCGTTGGCGGA	TCCGCCAACGCCCCGGCGA
730	CGCCGGGGCGTTGGCGGAA	TTCCGCCAACGCCCCGGCG
731	GCCGGGGCGTTGGCGGAAG	CTTCCGCCAACGCCCCGGC
732	CCGGGGCGTTGGCGGAAGC	GCTTCCGCCAACGCCCCGG
733	CGGGGCGTTGGCGGAAGCC	GGCTTCCGCCAACGCCCCG
734	GGGGCGTTGGCGGAAGCCC	GGGCTTCCGCCAACGCCCC
735	GGGCGTTGGCGGAAGCCCC	GGGGCTTCCGCCAACGCCC
736	GGCGTTGGCGGAAGCCCCC	GGGGGCTTCCGCCAACGCC
737	GCGTTGGCGGAAGCCCCCG	CGGGGGCTTCCGCCAACGC
738	CGTTGGCGGAAGCCCCCGG	CCGGGGGCTTCCGCCAACG
739	GTTGGCGGAAGCCCCCGGG	CCCGGGGGCTTCCGCCAAC
740	TTGGCGGAAGCCCCCGGGG	CCCCGGGGGCTTCCGCCAA
741	TGGCGGAAGCCCCCGGGGC	GCCCCGGGGGCTTCCGCCA
742	GGCGGAAGCCCCCGGGGCC	GGCCCCGGGGGCTTCCGCC
743	GCGGAAGCCCCCGGGGCCC	GGGCCCCGGGGGCTTCCGC
744	CGGAAGCCCCCGGGGCCCG	CGGGCCCCGGGGGCTTCCG
745	GGAAGCCCCCGGGGCCCGG	CCGGGCCCCGGGGGCTTCC
746	GAAGCCCCCGGGGCCCGGG	CCCGGGCCCCGGGGGCTTC
747	AAGCCCCCGGGGCCCGGGA	TCCCGGGCCCCGGGGGCTT
748	AGCCCCCGGGGCCCGGGAG	CTCCCGGGCCCCGGGGGCT
749	GCCCCCGGGGCCCGGGAGG	CCTCCCGGGCCCCGGGGGC
750	CCCCCGGGGCCCGGGAGGG	CCCTCCCGGGCCCCGGGGG
751	CCCCGGGGCCCGGGAGGGG	CCCCTCCCGGGCCCCGGGG
752	CCCGGGGCCCGGGAGGGGG	CCCCCTCCCGGGCCCCGGG
753	CCGGGGCCCGGGAGGGGGC	GCCCCCTCCCGGGCCCCGG
754	CGGGGCCCGGGAGGGGGCA	TGCCCCCTCCCGGGCCCCG
755	GGGGCCCGGGAGGGGGCAG	CTGCCCCCTCCCGGGCCCC
756	GGGCCCGGGAGGGGGCAGG	CCTGCCCCCTCCCGGGCCC
757	GGCCCGGGAGGGGGCAGGC	GCCTGCCCCCTCCCGGGCC
758	GCCCGGGAGGGGGCAGGCC	GGCCTGCCCCCTCCCGGGC
759	CCCGGGAGGGGGCAGGCCC	GGGCCTGCCCCCTCCCGGG
760	CCGGGAGGGGGCAGGCCCA	TGGGCCTGCCCCCTCCCGG
761	CGGGAGGGGGCAGGCCCAG	CTGGGCCTGCCCCCTCCCG
762	GGGAGGGGGCAGGCCCAGG	CCTGGGCCTGCCCCCTCCC
763	GGAGGGGGCAGGCCCAGGC	GCCTGGGCCTGCCCCCTCC
764	GAGGGGGCAGGCCCAGGCG	CGCCTGGGCCTGCCCCCTC
765	AGGGGGCAGGCCCAGGCGC	GCGCCTGGGCCTGCCCCCT
766	GGGGGCAGGCCCAGGCGCG	CGCGCCTGGGCCTGCCCCC
767	GGGGCAGGCCCAGGCGCGG	CCGCGCCTGGGCCTGCCCC
768	GGGCAGGCCCAGGCGCGGC	GCCGCGCCTGGGCCTGCCC
769	GGCAGGCCCAGGCGCGGCC	GGCCGCGCCTGGGCCTGCC
770	GCAGGCCCAGGCGCGGCCG	CGGCCGCGCCTGGGCCTGC
771	CAGGCCCAGGCGCGGCCGC	GCGGCCGCGCCTGGGCCTG
772	AGGCCCAGGCGCGGCCGCC	GGCGGCCGCGCCTGGGCCT
773	GGCCCAGGCGCGGCCGCCG	CGGCGGCCGCGCCTGGGCC
774	GCCCAGGCGCGGCCGCCGA	TCGGCGGCCGCGCCTGGGC
775	CCCAGGCGCGGCCGCCGAA	TTCGGCGGCCGCGCCTGGG
776	CCAGGCGCGGCCGCCGAAT	ATTCGGCGGCCGCGCCTGG
777	CAGGCGCGGCCGCCGAATC	GATTCGGCGGCCGCGCCTG
778	AGGCGCGGCCGCCGAATCA	TGATTCGGCGGCCGCGCCT
779	GGCGCGGCCGCCGAATCAC	GTGATTCGGCGGCCGCGCC
780	GCGCGGCCGCCGAATCACG	CGTGATTCGGCGGCCGCGC
781	CGCGGCCGCCGAATCACGG	CCGTGATTCGGCGGCCGCG
782	GCGGCCGCCGAATCACGGG	CCCGTGATTCGGCGGCCGC
783	CGGCCGCCGAATCACGGGC	GCCCGTGATTCGGCGGCCG
784	GGCCGCCGAATCACGGGCT	AGCCCGTGATTCGGCGGCC
785	GCCGCCGAATCACGGGCTC	GAGCCCGTGATTCGGCGGC
786	CCGCCGAATCACGGGCTCC	GGAGCCCGTGATTCGGCGG
787	CGCCGAATCACGGGCTCCT	AGGAGCCCGTGATTCGGCG
788	GCCGAATCACGGGCTCCTG	CAGGAGCCCGTGATTCGGC
789	CCGAATCACGGGCTCCTGT	ACAGGAGCCCGTGATTCGG
790	CGAATCACGGGCTCCTGTT	AACAGGAGCCCGTGATTCG
791	GAATCACGGGCTCCTGTTT	AAACAGGAGCCCGTGATTC
792	AATCACGGGCTCCTGTTTC	GAAACAGGAGCCCGTGATT
793	ATCACGGGCTCCTGTTTCC	GGAAACAGGAGCCCGTGAT
794	TCACGGGCTCCTGTTTCCC	GGGAAACAGGAGCCCGTGA
795	CACGGGCTCCTGTTTCCCG	CGGGAAACAGGAGCCCGTG
796	ACGGGCTCCTGTTTCCCGC	GCGGGAAACAGGAGCCCGT
797	CGGGCTCCTGTTTCCCGCA	TGCGGGAAACAGGAGCCCG
798	GGGCTCCTGTTTCCCGCAG	CTGCGGGAAACAGGAGCCC
799	GGCTCCTGTTTCCCGCAGG	CCTGCGGGAAACAGGAGCC
800	GCTCCTGTTTCCCGCAGGG	CCCTGCGGGAAACAGGAGC
801	CTCCTGTTTCCCGCAGGGT	ACCCTGCGGGAAACAGGAG
802	TCCTGTTTCCCGCAGGGTG	CACCCTGCGGGAAACAGGA
803	CCTGTTTCCCGCAGGGTGC	GCACCCTGCGGGAAACAGG
804	CTGTTTCCCGCAGGGTGCT	AGCACCCTGCGGGAAACAG
805	TGTTTCCCGCAGGGTGCTG	CAGCACCCTGCGGGAAACA
806	GTTTCCCGCAGGGTGCTGG	CCAGCACCCTGCGGGAAAC
807	TTTCCCGCAGGGTGCTGGA	TCCAGCACCCTGCGGGAAA
808	TTCCCGCAGGGTGCTGGAG	CTCCAGCACCCTGCGGGAA
809	TCCCGCAGGGTGCTGGAGG	CCTCCAGCACCCTGCGGGA
810	CCCGCAGGGTGCTGGAGGA	TCCTCCAGCACCCTGCGGG
811	CCGCAGGGTGCTGGAGGAG	CTCCTCCAGCACCCTGCGG
812	CGCAGGGTGCTGGAGGAGG	CCTCCTCCAGCACCCTGCG
813	GCAGGGTGCTGGAGGAGGA	TCCTCCTCCAGCACCCTGC
814	CAGGGTGCTGGAGGAGGAA	TTCCTCCTCCAGCACCCTG
815	AGGGTGCTGGAGGAGGAAA	TTTCCTCCTCCAGCACCCT
816	GGGTGCTGGAGGAGGAAAC	GTTTCCTCCTCCAGCACCC
817	GGTGCTGGAGGAGGAAACC	GGTTTCCTCCTCCAGCACC
818	GTGCTGGAGGAGGAAACCG	CGGTTTCCTCCTCCAGCAC
819	TGCTGGAGGAGGAAACCGG	CCGGTTTCCTCCTCCAGCA
820	GCTGGAGGAGGAAACCGGC	GCCGGTTTCCTCCTCCAGC
821	CTGGAGGAGGAAACCGGCG	CGCCGGTTTCCTCCTCCAG
822	TGGAGGAGGAAACCGGCGG	CCGCCGGTTTCCTCCTCCA
823	GGAGGAGGAAACCGGCGGA	TCCGCCGGTTTCCTCCTCC
824	GAGGAGGAAACCGGCGGAG	CTCCGCCGGTTTCCTCCTC
825	AGGAGGAAACCGGCGGAGC	GCTCCGCCGGTTTCCTCCT
826	GGAGGAAACCGGCGGAGCA	TGCTCCGCCGGTTTCCTCC
827	GAGGAAACCGGCGGAGCAG	CTGCTCCGCCGGTTTCCTC
828	AGGAAACCGGCGGAGCAGC	GCTGCTCCGCCGGTTTCCT
829	GGAAACCGGCGGAGCAGCT	AGCTGCTCCGCCGGTTTCC
830	GAAACCGGCGGAGCAGCTT	AAGCTGCTCCGCCGGTTTC
831	AAACCGGCGGAGCAGCTTC	GAAGCTGCTCCGCCGGTTT
832	AACCGGCGGAGCAGCTTCC	GGAAGCTGCTCCGCCGGTT
833	ACCGGCGGAGCAGCTTCCC	GGGAAGCTGCTCCGCCGGT
834	CCGGCGGAGCAGCTTCCCC	GGGGAAGCTGCTCCGCCGG
835	CGGCGGAGCAGCTTCCCCA	TGGGGAAGCTGCTCCGCCG
836	GGCGGAGCAGCTTCCCCAC	GTGGGGAAGCTGCTCCGCC
837	GCGGAGCAGCTTCCCCACT	AGTGGGGAAGCTGCTCCGC
838	CGGAGCAGCTTCCCCACTC	GAGTGGGGAAGCTGCTCCG
839	GGAGCAGCTTCCCCACTCT	AGAGTGGGGAAGCTGCTCC
840	GAGCAGCTTCCCCACTCTC	GAGAGTGGGGAAGCTGCTC
841	AGCAGCTTCCCCACTCTCA	TGAGAGTGGGGAAGCTGCT
842	GCAGCTTCCCCACTCTCAG	CTGAGAGTGGGGAAGCTGC
843	CAGCTTCCCCACTCTCAGT	ACTGAGAGTGGGGAAGCTG
844	AGCTTCCCCACTCTCAGTT	AACTGAGAGTGGGGAAGCT
845	GCTTCCCCACTCTCAGTTG	CAACTGAGAGTGGGGAAGC
846	CTTCCCCACTCTCAGTTGC	GCAACTGAGAGTGGGGAAG
847	TTCCCCACTCTCAGTTGCG	CGCAACTGAGAGTGGGGAA
848	TCCCCACTCTCAGTTGCGC	GCGCAACTGAGAGTGGGGA
849	CCCCACTCTCAGTTGCGCT	AGCGCAACTGAGAGTGGGG
850	CCCACTCTCAGTTGCGCTT	AAGCGCAACTGAGAGTGGG
851	CCACTCTCAGTTGCGCTTC	GAAGCGCAACTGAGAGTGG
852	CACTCTCAGTTGCGCTTCT	AGAAGCGCAACTGAGAGTG
853	ACTCTCAGTTGCGCTTCTG	CAGAAGCGCAACTGAGAGT
854	CTCTCAGTTGCGCTTCTGG	CCAGAAGCGCAACTGAGAG
855	TCTCAGTTGCGCTTCTGGC	GCCAGAAGCGCAACTGAGA
856	CTCAGTTGCGCTTCTGGCG	CGCCAGAAGCGCAACTGAG
857	TCAGTTGCGCTTCTGGCGA	TCGCCAGAAGCGCAACTGA
858	CAGTTGCGCTTCTGGCGAT	ATCGCCAGAAGCGCAACTG
859	AGTTGCGCTTCTGGCGATG	CATCGCCAGAAGCGCAACT
860	GTTGCGCTTCTGGCGATGG	CCATCGCCAGAAGCGCAAC
861	TTGCGCTTCTGGCGATGGC	GCCATCGCCAGAAGCGCAA
862	TGCGCTTCTGGCGATGGCG	CGCCATCGCCAGAAGCGCA
863	GCGCTTCTGGCGATGGCGA	TCGCCATCGCCAGAAGCGC
864	CGCTTCTGGCGATGGCGAT	ATCGCCATCGCCAGAAGCG
865	GCTTCTGGCGATGGCGATC	GATCGCCATCGCCAGAAGC
866	CTTCTGGCGATGGCGATCA	TGATCGCCATCGCCAGAAG
867	TTCTGGCGATGGCGATCAG	CTGATCGCCATCGCCAGAA
868	TCTGGCGATGGCGATCAGA	TCTGATCGCCATCGCCAGA
869	CTGGCGATGGCGATCAGAG	CTCTGATCGCCATCGCCAG
870	TGGCGATGGCGATCAGAGG	CCTCTGATCGCCATCGCCA
871	GGCGATGGCGATCAGAGGT	ACCTCTGATCGCCATCGCC
872	GCGATGGCGATCAGAGGTC	GACCTCTGATCGCCATCGC
873	CGATGGCGATCAGAGGTCC	GGACCTCTGATCGCCATCG
874	GATGGCGATCAGAGGTCCT	AGGACCTCTGATCGCCATC
875	ATGGCGATCAGAGGTCCTG	CAGGACCTCTGATCGCCAT
876	TGGCGATCAGAGGTCCTGC	GCAGGACCTCTGATCGCCA
877	GGCGATCAGAGGTCCTGCT	AGCAGGACCTCTGATCGCC
878	GCGATCAGAGGTCCTGCTG	CAGCAGGACCTCTGATCGC
879	CGATCAGAGGTCCTGCTGC	GCAGCAGGACCTCTGATCG
880	GATCAGAGGTCCTGCTGCG	CGCAGCAGGACCTCTGATC
881	ATCAGAGGTCCTGCTGCGC	GCGCAGCAGGACCTCTGAT
882	TCAGAGGTCCTGCTGCGCT	AGCGCAGCAGGACCTCTGA
883	CAGAGGTCCTGCTGCGCTC	GAGCGCAGCAGGACCTCTG
884	AGAGGTCCTGCTGCGCTCT	AGAGCGCAGCAGGACCTCT
885	GAGGTCCTGCTGCGCTCTC	GAGAGCGCAGCAGGACCTC
886	AGGTCCTGCTGCGCTCTCC	GGAGAGCGCAGCAGGACCT
887	GGTCCTGCTGCGCTCTCCG	CGGAGAGCGCAGCAGGACC
888	GTCCTGCTGCGCTCTCCGC	GCGGAGAGCGCAGCAGGAC
889	TCCTGCTGCGCTCTCCGCC	GGCGGAGAGCGCAGCAGGA
890	CCTGCTGCGCTCTCCGCCG	CGGCGGAGAGCGCAGCAGG
891	CTGCTGCGCTCTCCGCCGC	GCGGCGGAGAGCGCAGCAG
892	TGCTGCGCTCTCCGCCGCG	CGCGGCGGAGAGCGCAGCA
893	GCTGCGCTCTCCGCCGCGC	GCGCGGCGGAGAGCGCAGC
894	CTGCGCTCTCCGCCGCGCT	AGCGCGGCGGAGAGCGCAG
895	TGCGCTCTCCGCCGCGCTC	GAGCGCGGCGGAGAGCGCA
896	GCGCTCTCCGCCGCGCTCT	AGAGCGCGGCGGAGAGCGC
897	CGCTCTCCGCCGCGCTCTA	TAGAGCGCGGCGGAGAGCG
898	GCTCTCCGCCGCGCTCTAC	GTAGAGCGCGGCGGAGAGC
899	CTCTCCGCCGCGCTCTACC	GGTAGAGCGCGGCGGAGAG
900	TCTCCGCCGCGCTCTACCT	AGGTAGAGCGCGGCGGAGA
901	CTCCGCCGCGCTCTACCTC	GAGGTAGAGCGCGGCGGAG
902	TCCGCCGCGCTCTACCTCC	GGAGGTAGAGCGCGGCGGA
903	CCGCCGCGCTCTACCTCCA	TGGAGGTAGAGCGCGGCGG
904	CGCCGCGCTCTACCTCCAT	ATGGAGGTAGAGCGCGGCG
905	GCCGCGCTCTACCTCCATT	AATGGAGGTAGAGCGCGGC
906	CCGCGCTCTACCTCCATTA	TAATGGAGGTAGAGCGCGG
907	CGCGCTCTACCTCCATTAG	CTAATGGAGGTAGAGCGCG
908	GCGCTCTACCTCCATTAGC	GCTAATGGAGGTAGAGCGC
909	CGCTCTACCTCCATTAGCC	GGCTAATGGAGGTAGAGCG
910	GCTCTACCTCCATTAGCCG	CGGCTAATGGAGGTAGAGC
911	CTCTACCTCCATTAGCCGC	GCGGCTAATGGAGGTAGAG
912	TCTACCTCCATTAGCCGCG	CGCGGCTAATGGAGGTAGA
913	CTACCTCCATTAGCCGCGC	GCGCGGCTAATGGAGGTAG
914	TACCTCCATTAGCCGCGCT	AGCGCGGCTAATGGAGGTA
915	ACCTCCATTAGCCGCGCTG	CAGCGCGGCTAATGGAGGT
916	CCTCCATTAGCCGCGCTGC	GCAGCGCGGCTAATGGAGG
917	CTCCATTAGCCGCGCTGCG	CGCAGCGCGGCTAATGGAG
918	TCCATTAGCCGCGCTGCGC	GCGCAGCGCGGCTAATGGA
919	CCATTAGCCGCGCTGCGCG	CGCGCAGCGCGGCTAATGG
920	CATTAGCCGCGCTGCGCGG	CCGCGCAGCGCGGCTAATG
921	ATTAGCCGCGCTGCGCGGT	ACCGCGCAGCGCGGCTAAT
922	TTAGCCGCGCTGCGCGGTG	CACCGCGCAGCGCGGCTAA
923	TAGCCGCGCTGCGCGGTGC	GCACCGCGCAGCGCGGCTA
924	AGCCGCGCTGCGCGGTGCT	AGCACCGCGCAGCGCGGCT
925	GCCGCGCTGCGCGGTGCTG	CAGCACCGCGCAGCGCGGC
926	CCGCGCTGCGCGGTGCTGC	GCAGCACCGCGCAGCGCGG
927	CGCGCTGCGCGGTGCTGCG	CGCAGCACCGCGCAGCGCG
928	GCGCTGCGCGGTGCTGCGC	GCGCAGCACCGCGCAGCGC
929	CGCTGCGCGGTGCTGCGCC	GGCGCAGCACCGCGCAGCG
930	GCTGCGCGGTGCTGCGCCC	GGGCGCAGCACCGCGCAGC
931	CTGCGCGGTGCTGCGCCCT	AGGGCGCAGCACCGCGCAG
932	TGCGCGGTGCTGCGCCCTC	GAGGGCGCAGCACCGCGCA
933	GCGCGGTGCTGCGCCCTCG	CGAGGGCGCAGCACCGCGC
934	CGCGGTGCTGCGCCCTCGC	GCGAGGGCGCAGCACCGCG
935	GCGGTGCTGCGCCCTCGCC	GGCGAGGGCGCAGCACCGC
936	CGGTGCTGCGCCCTCGCCG	CGGCGAGGGCGCAGCACCG
937	GGTGCTGCGCCCTCGCCGG	CCGGCGAGGGCGCAGCACC
938	GTGCTGCGCCCTCGCCGGT	ACCGGCGAGGGCGCAGCAC
939	TGCTGCGCCCTCGCCGGTG	CACCGGCGAGGGCGCAGCA
940	GCTGCGCCCTCGCCGGTGC	GCACCGGCGAGGGCGCAGC
941	CTGCGCCCTCGCCGGTGCC	GGCACCGGCGAGGGCGCAG
942	TGCGCCCTCGCCGGTGCCT	AGGCACCGGCGAGGGCGCA
943	GCGCCCTCGCCGGTGCCTC	GAGGCACCGGCGAGGGCGC
944	CGCCCTCGCCGGTGCCTCT	AGAGGCACCGGCGAGGGCG
945	GCCCTCGCCGGTGCCTCTC	GAGAGGCACCGGCGAGGGC
946	CCCTCGCCGGTGCCTCTCT	AGAGAGGCACCGGCGAGGG
947	CCTCGCCGGTGCCTCTCTC	GAGAGAGGCACCGGCGAGG
948	CTCGCCGGTGCCTCTCTCC	GGAGAGAGGCACCGGCGAG
949	TCGCCGGTGCCTCTCTCCT	AGGAGAGAGGCACCGGCGA
950	CGCCGGTGCCTCTCTCCTG	CAGGAGAGAGGCACCGGCG
951	GCCGGTGCCTCTCTCCTGG	CCAGGAGAGAGGCACCGGC
952	CCGGTGCCTCTCTCCTGGG	CCCAGGAGAGAGGCACCGG
953	CGGTGCCTCTCTCCTGGGT	ACCCAGGAGAGAGGCACCG
954	GGTGCCTCTCTCCTGGGTC	GACCCAGGAGAGAGGCACC
955	GTGCCTCTCTCCTGGGTCC	GGACCCAGGAGAGAGGCAC
956	TGCCTCTCTCCTGGGTCCC	GGGACCCAGGAGAGAGGCA
957	GCCTCTCTCCTGGGTCCCA	TGGGACCCAGGAGAGAGGC
958	CCTCTCTCCTGGGTCCCAG	CTGGGACCCAGGAGAGAGG
959	CTCTCTCCTGGGTCCCAGG	CCTGGGACCCAGGAGAGAG
960	TCTCTCCTGGGTCCCAGGA	TCCTGGGACCCAGGAGAGA
961	CTCTCCTGGGTCCCAGGAT	ATCCTGGGACCCAGGAGAG
962	TCTCCTGGGTCCCAGGATC	GATCCTGGGACCCAGGAGA
963	CTCCTGGGTCCCAGGATCG	CGATCCTGGGACCCAGGAG
964	TCCTGGGTCCCAGGATCGG	CCGATCCTGGGACCCAGGA
965	CCTGGGTCCCAGGATCGGC	GCCGATCCTGGGACCCAGG
966	CTGGGTCCCAGGATCGGCC	GGCCGATCCTGGGACCCAG
967	TGGGTCCCAGGATCGGCCC	GGGCCGATCCTGGGACCCA
968	GGGTCCCAGGATCGGCCCC	GGGGCCGATCCTGGGACCC
969	GGTCCCAGGATCGGCCCCC	GGGGGCCGATCCTGGGACC
970	GTCCCAGGATCGGCCCCCA	TGGGGGCCGATCCTGGGAC
971	TCCCAGGATCGGCCCCCAC	GTGGGGGCCGATCCTGGGA
972	CCCAGGATCGGCCCCCACC	GGTGGGGGCCGATCCTGGG
973	CCAGGATCGGCCCCCACCA	TGGTGGGGGCCGATCCTGG
974	CAGGATCGGCCCCCACCAT	ATGGTGGGGGCCGATCCTG
975	AGGATCGGCCCCCACCATC	GATGGTGGGGGCCGATCCT
976	GGATCGGCCCCCACCATCC	GGATGGTGGGGGCCGATCC
977	GATCGGCCCCCACCATCCA	TGGATGGTGGGGGCCGATC
978	ATCGGCCCCCACCATCCAG	CTGGATGGTGGGGGCCGAT
979	TCGGCCCCCACCATCCAGG	CCTGGATGGTGGGGGCCGA
980	CGGCCCCCACCATCCAGGC	GCCTGGATGGTGGGGGCCG
981	GGCCCCCACCATCCAGGCA	TGCCTGGATGGTGGGGGCC
982	GCCCCCACCATCCAGGCAC	GTGCCTGGATGGTGGGGGC
983	CCCCCACCATCCAGGCACG	CGTGCCTGGATGGTGGGGG
984	CCCCACCATCCAGGCACGA	TCGTGCCTGGATGGTGGGG
985	CCCACCATCCAGGCACGAC	GTCGTGCCTGGATGGTGGG
986	CCACCATCCAGGCACGACC	GGTCGTGCCTGGATGGTGG
987	CACCATCCAGGCACGACCC	GGGTCGTGCCTGGATGGTG
988	ACCATCCAGGCACGACCCC	GGGGTCGTGCCTGGATGGT
989	CCATCCAGGCACGACCCCC	GGGGGTCGTGCCTGGATGG
990	CATCCAGGCACGACCCCCT	AGGGGGTCGTGCCTGGATG
991	ATCCAGGCACGACCCCCTT	AAGGGGGTCGTGCCTGGAT
992	TCCAGGCACGACCCCCTTC	GAAGGGGGTCGTGCCTGGA
993	CCAGGCACGACCCCCTTCC	GGAAGGGGGTCGTGCCTGG
994	CAGGCACGACCCCCTTCCC	GGGAAGGGGGTCGTGCCTG
995	AGGCACGACCCCCTTCCCC	GGGGAAGGGGGTCGTGCCT
996	GGCACGACCCCCTTCCCCG	CGGGGAAGGGGGTCGTGCC
997	GCACGACCCCCTTCCCCGG	CCGGGGAAGGGGGTCGTGC
998	CACGACCCCCTTCCCCGGC	GCCGGGGAAGGGGGTCGTG
999	ACGACCCCCTTCCCCGGCC	GGCCGGGGAAGGGGGTCGT
1000	CGACCCCCTTCCCCGGCCC	GGGCCGGGGAAGGGGGTCG
1001	GACCCCCTTCCCCGGCCCC	GGGGCCGGGGAAGGGGGTC
1002	ACCCCCTTCCCCGGCCCCT	AGGGGCCGGGGAAGGGGGT
1003	CCCCCTTCCCCGGCCCCTC	GAGGGGCCGGGGAAGGGGG
1004	CCCCTTCCCCGGCCCCTCG	CGAGGGGCCGGGGAAGGGG
1005	CCCTTCCCCGGCCCCTCGG	CCGAGGGGCCGGGGAAGGG
1006	CCTTCCCCGGCCCCTCGGC	GCCGAGGGGCCGGGGAAGG
1007	CTTCCCCGGCCCCTCGGCC	GGCCGAGGGGCCGGGGAAG
1008	TTCCCCGGCCCCTCGGCCT	AGGCCGAGGGGCCGGGGAA
1009	TCCCCGGCCCCTCGGCCTT	AAGGCCGAGGGGCCGGGGA
1010	CCCCGGCCCCTCGGCCTTT	AAAGGCCGAGGGGCCGGGG
1011	CCCGGCCCCTCGGCCTTTC	GAAAGGCCGAGGGGCCGGG
1012	CCGGCCCCTCGGCCTTTCC	GGAAAGGCCGAGGGGCCGG
1013	CGGCCCCTCGGCCTTTCCC	GGGAAAGGCCGAGGGGCCG
1014	GGCCCCTCGGCCTTTCCCC	GGGGAAAGGCCGAGGGGCC
1015	GCCCCTCGGCCTTTCCCCC	GGGGGAAAGGCCGAGGGGC
1016	CCCCTCGGCCTTTCCCCCA	TGGGGGAAAGGCCGAGGGG
1017	CCCTCGGCCTTTCCCCCAA	TTGGGGGAAAGGCCGAGGG
1018	CCTCGGCCTTTCCCCCAAC	GTTGGGGGAAAGGCCGAGG
1019	CTCGGCCTTTCCCCCAACT	AGTTGGGGGAAAGGCCGAG
1020	TCGGCCTTTCCCCCAACTC	GAGTTGGGGGAAAGGCCGA
1021	CGGCCTTTCCCCCAACTCG	CGAGTTGGGGGAAAGGCCG
1022	GGCCTTTCCCCCAACTCGG	CCGAGTTGGGGGAAAGGCC
1023	GCCTTTCCCCCAACTCGGC	GCCGAGTTGGGGGAAAGGC
1024	CCTTTCCCCCAACTCGGCC	GGCCGAGTTGGGGGAAAGG
1025	CTTTCCCCCAACTCGGCCA	TGGCCGAGTTGGGGGAAAG
1026	TTTCCCCCAACTCGGCCAT	ATGGCCGAGTTGGGGGAAA
1027	TTCCCCCAACTCGGCCATC	GATGGCCGAGTTGGGGGAA
1028	TCCCCCAACTCGGCCATCT	AGATGGCCGAGTTGGGGGA
1029	CCCCCAACTCGGCCATCTC	GAGATGGCCGAGTTGGGGG
1030	CCCCAACTCGGCCATCTCC	GGAGATGGCCGAGTTGGGG
1031	CCCAACTCGGCCATCTCCG	CGGAGATGGCCGAGTTGGG
1032	CCAACTCGGCCATCTCCGA	TCGGAGATGGCCGAGTTGG
1033	CAACTCGGCCATCTCCGAC	GTCGGAGATGGCCGAGTTG
1034	AACTCGGCCATCTCCGACC	GGTCGGAGATGGCCGAGTT
1035	ACTCGGCCATCTCCGACCC	GGGTCGGAGATGGCCGAGT
1036	CTCGGCCATCTCCGACCCG	CGGGTCGGAGATGGCCGAG
1037	TCGGCCATCTCCGACCCGG	CCGGGTCGGAGATGGCCGA
1038	CGGCCATCTCCGACCCGGG	CCCGGGTCGGAGATGGCCG
1039	GGCCATCTCCGACCCGGGG	CCCCGGGTCGGAGATGGCC
1040	GCCATCTCCGACCCGGGGC	GCCCCGGGTCGGAGATGGC
1041	CCATCTCCGACCCGGGGCG	CGCCCCGGGTCGGAGATGG
1042	CATCTCCGACCCGGGGCGC	GCGCCCCGGGTCGGAGATG
1043	ATCTCCGACCCGGGGCGCG	CGCGCCCCGGGTCGGAGAT
1044	TCTCCGACCCGGGGCGCGT	ACGCGCCCCGGGTCGGAGA
1045	CTCCGACCCGGGGCGCGTG	CACGCGCCCCGGGTCGGAG
1046	TCCGACCCGGGGCGCGTGT	ACACGCGCCCCGGGTCGGA
1047	CCGACCCGGGGCGCGTGTT	AACACGCGCCCCGGGTCGG
1048	CGACCCGGGGCGCGTGTTC	GAACACGCGCCCCGGGTCG
1049	GACCCGGGGCGCGTGTTCC	GGAACACGCGCCCCGGGTC
1050	ACCCGGGGCGCGTGTTCCC	GGGAACACGCGCCCCGGGT
1051	CCCGGGGCGCGTGTTCCCC	GGGGAACACGCGCCCCGGG
1052	CCGGGGCGCGTGTTCCCCC	GGGGGAACACGCGCCCCGG
1053	CGGGGCGCGTGTTCCCCCC	GGGGGGAACACGCGCCCCG
1054	GGGGCGCGTGTTCCCCCCG	CGGGGGGAACACGCGCCCC
1055	GGGCGCGTGTTCCCCCCGG	CCGGGGGGAACACGCGCCC
1056	GGCGCGTGTTCCCCCCGGC	GCCGGGGGGAACACGCGCC
1057	GCGCGTGTTCCCCCCGGCC	GGCCGGGGGGAACACGCGC
1058	CGCGTGTTCCCCCCGGCCC	GGGCCGGGGGGAACACGCG
1059	GCGTGTTCCCCCCGGCCCG	CGGGCCGGGGGGAACACGC
1060	CGTGTTCCCCCCGGCCCGG	CCGGGCCGGGGGGAACACG
1061	GTGTTCCCCCCGGCCCGGC	GCCGGGCCGGGGGGAACAC
1062	TGTTCCCCCCGGCCCGGCG	CGCCGGGCCGGGGGGAACA
1063	GTTCCCCCCGGCCCGGCGC	GCGCCGGGCCGGGGGGAAC
1064	TTCCCCCCGGCCCGGCGCC	GGCGCCGGGCCGGGGGGAA
1065	TCCCCCCGGCCCGGCGCCT	AGGCGCCGGGCCGGGGGGA
1066	CCCCCCGGCCCGGCGCCTT	AAGGCGCCGGGCCGGGGGG
1067	CCCCCGGCCCGGCGCCTTC	GAAGGCGCCGGGCCGGGGG
1068	CCCCGGCCCGGCGCCTTCT	AGAAGGCGCCGGGCCGGGG
1069	CCCGGCCCGGCGCCTTCTC	GAGAAGGCGCCGGGCCGGG
1070	CCGGCCCGGCGCCTTCTCT	AGAGAAGGCGCCGGGCCGG
1071	CGGCCCGGCGCCTTCTCTC	GAGAGAAGGCGCCGGGCCG
1072	GGCCCGGCGCCTTCTCTCC	GGAGAGAAGGCGCCGGGCC
1073	GCCCGGCGCCTTCTCTCCC	GGGAGAGAAGGCGCCGGGC
1074	CCCGGCGCCTTCTCTCCCT	AGGGAGAGAAGGCGCCGGG
1075	CCGGCGCCTTCTCTCCCTC	GAGGGAGAGAAGGCGCCGG
1076	CGGCGCCTTCTCTCCCTCC	GGAGGGAGAGAAGGCGCCG
1077	GGCGCCTTCTCTCCCTCCG	CGGAGGGAGAGAAGGCGCC
1078	GCGCCTTCTCTCCCTCCGG	CCGGAGGGAGAGAAGGCGC
1079	CGCCTTCTCTCCCTCCGGG	CCCGGAGGGAGAGAAGGCG
1080	GCCTTCTCTCCCTCCGGGG	CCCCGGAGGGAGAGAAGGC
1081	CCTTCTCTCCCTCCGGGGG	CCCCCGGAGGGAGAGAAGG
1082	CTTCTCTCCCTCCGGGGGC	GCCCCCGGAGGGAGAGAAG
1083	TTCTCTCCCTCCGGGGGCA	TGCCCCCGGAGGGAGAGAA
1084	TCTCTCCCTCCGGGGGCAC	GTGCCCCCGGAGGGAGAGA
1085	CTCTCCCTCCGGGGGCACC	GGTGCCCCCGGAGGGAGAG
1086	TCTCCCTCCGGGGGCACCC	GGGTGCCCCCGGAGGGAGA
1087	CTCCCTCCGGGGGCACCCG	CGGGTGCCCCCGGAGGGAG
1088	TCCCTCCGGGGGCACCCGC	GCGGGTGCCCCCGGAGGGA
1089	CCCTCCGGGGGCACCCGCT	AGCGGGTGCCCCCGGAGGG
1090	CCTCCGGGGGCACCCGCTC	GAGCGGGTGCCCCCGGAGG
1091	CTCCGGGGGCACCCGCTCC	GGAGCGGGTGCCCCCGGAG
1092	TCCGGGGGCACCCGCTCCC	GGGAGCGGGTGCCCCCGGA
1093	CCGGGGGCACCCGCTCCCT	AGGGAGCGGGTGCCCCCGG
1094	CGGGGGCACCCGCTCCCTA	TAGGGAGCGGGTGCCCCCG
1095	GGGGGCACCCGCTCCCTAG	CTAGGGAGCGGGTGCCCCC
1096	GGGGCACCCGCTCCCTAGC	GCTAGGGAGCGGGTGCCCC
1097	GGGCACCCGCTCCCTAGCC	GGCTAGGGAGCGGGTGCCC
1098	GGCACCCGCTCCCTAGCCC	GGGCTAGGGAGCGGGTGCC
1099	GCACCCGCTCCCTAGCCCC	GGGGCTAGGGAGCGGGTGC
1100	CACCCGCTCCCTAGCCCCG	CGGGGCTAGGGAGCGGGTG
1101	ACCCGCTCCCTAGCCCCGG	CCGGGGCTAGGGAGCGGGT
1102	CCCGCTCCCTAGCCCCGGC	GCCGGGGCTAGGGAGCGGG
1103	CCGCTCCCTAGCCCCGGCC	GGCCGGGGCTAGGGAGCGG
1104	CGCTCCCTAGCCCCGGCCC	GGGCCGGGGCTAGGGAGCG
1105	GCTCCCTAGCCCCGGCCCG	CGGGCCGGGGCTAGGGAGC
1106	CTCCCTAGCCCCGGCCCGG	CCGGGCCGGGGCTAGGGAG
1107	TCCCTAGCCCCGGCCCGGC	GCCGGGCCGGGGCTAGGGA
1108	CCCTAGCCCCGGCCCGGCC	GGCCGGGCCGGGGCTAGGG
1109	CCTAGCCCCGGCCCGGCCC	GGGCCGGGCCGGGGCTAGG
1110	CTAGCCCCGGCCCGGCCCT	AGGGCCGGGCCGGGGCTAG
1111	TAGCCCCGGCCCGGCCCTC	GAGGGCCGGGCCGGGGCTA
1112	AGCCCCGGCCCGGCCCTCC	GGAGGGCCGGGCCGGGGCT
1113	GCCCCGGCCCGGCCCTCCC	GGGAGGGCCGGGCCGGGGC
1114	CCCCGGCCCGGCCCTCCCC	GGGGAGGGCCGGGCCGGGG
1115	CCCGGCCCGGCCCTCCCCG	CGGGGAGGGCCGGGCCGGG
1116	CCGGCCCGGCCCTCCCCGC	GCGGGGAGGGCCGGGCCGG
1117	CGGCCCGGCCCTCCCCGCG	CGCGGGGAGGGCCGGGCCG
1118	GGCCCGGCCCTCCCCGCGG	CCGCGGGGAGGGCCGGGCC
1119	GCCCGGCCCTCCCCGCGGC	GCCGCGGGGAGGGCCGGGC
1120	CCCGGCCCTCCCCGCGGCG	CGCCGCGGGGAGGGCCGGG
1121	CCGGCCCTCCCCGCGGCGC	GCGCCGCGGGGAGGGCCGG
1122	CGGCCCTCCCCGCGGCGCA	TGCGCCGCGGGGAGGGCCG
1123	GGCCCTCCCCGCGGCGCAG	CTGCGCCGCGGGGAGGGCC
1124	GCCCTCCCCGCGGCGCAGC	GCTGCGCCGCGGGGAGGGC
1125	CCCTCCCCGCGGCGCAGCA	TGCTGCGCCGCGGGGAGGG
1126	CCTCCCCGCGGCGCAGCAC	GTGCTGCGCCGCGGGGAGG
1127	CTCCCCGCGGCGCAGCACG	CGTGCTGCGCCGCGGGGAG
1128	TCCCCGCGGCGCAGCACGG	CCGTGCTGCGCCGCGGGGA
1129	CCCCGCGGCGCAGCACGGA	TCCGTGCTGCGCCGCGGGG
1130	CCCGCGGCGCAGCACGGAG	CTCCGTGCTGCGCCGCGGG
1131	CCGCGGCGCAGCACGGAGT	ACTCCGTGCTGCGCCGCGG
1132	CGCGGCGCAGCACGGAGTC	GACTCCGTGCTGCGCCGCG
1133	GCGGCGCAGCACGGAGTCT	AGACTCCGTGCTGCGCCGC
1134	CGGCGCAGCACGGAGTCTC	GAGACTCCGTGCTGCGCCG
1135	GGCGCAGCACGGAGTCTCG	CGAGACTCCGTGCTGCGCC
1136	GCGCAGCACGGAGTCTCGG	CCGAGACTCCGTGCTGCGC
1137	CGCAGCACGGAGTCTCGGC	GCCGAGACTCCGTGCTGCG
1138	GCAGCACGGAGTCTCGGCG	CGCCGAGACTCCGTGCTGC
1139	CAGCACGGAGTCTCGGCGT	ACGCCGAGACTCCGTGCTG
1140	AGCACGGAGTCTCGGCGTC	GACGCCGAGACTCCGTGCT
1141	GCACGGAGTCTCGGCGTCC	GGACGCCGAGACTCCGTGC
1142	CACGGAGTCTCGGCGTCCC	GGGACGCCGAGACTCCGTG
1143	ACGGAGTCTCGGCGTCCCA	TGGGACGCCGAGACTCCGT
1144	CGGAGTCTCGGCGTCCCAT	ATGGGACGCCGAGACTCCG
1145	GGAGTCTCGGCGTCCCATG	CATGGGACGCCGAGACTCC
1146	GAGTCTCGGCGTCCCATGG	CCATGGGACGCCGAGACTC
1147	AGTCTCGGCGTCCCATGGC	GCCATGGGACGCCGAGACT
1148	GTCTCGGCGTCCCATGGCG	CGCCATGGGACGCCGAGAC
1149	TCTCGGCGTCCCATGGCGC	GCGCCATGGGACGCCGAGA
1150	CTCGGCGTCCCATGGCGCA	TGCGCCATGGGACGCCGAG
1151	TCGGCGTCCCATGGCGCAA	TTGCGCCATGGGACGCCGA
1152	CGGCGTCCCATGGCGCAAC	GTTGCGCCATGGGACGCCG
1153	GGCGTCCCATGGCGCAACC	GGTTGCGCCATGGGACGCC
1154	GCGTCCCATGGCGCAACCT	AGGTTGCGCCATGGGACGC
1155	CGTCCCATGGCGCAACCTA	TAGGTTGCGCCATGGGACG
1156	GTCCCATGGCGCAACCTAC	GTAGGTTGCGCCATGGGAC
1157	TCCCATGGCGCAACCTACG	CGTAGGTTGCGCCATGGGA
1158	CCCATGGCGCAACCTACGG	CCGTAGGTTGCGCCATGGG
1159	CCATGGCGCAACCTACGGC	GCCGTAGGTTGCGCCATGG
1160	CATGGCGCAACCTACGGCC	GGCCGTAGGTTGCGCCATG
1161	ATGGCGCAACCTACGGCCT	AGGCCGTAGGTTGCGCCAT
1162	TGGCGCAACCTACGGCCTC	GAGGCCGTAGGTTGCGCCA
1163	GGCGCAACCTACGGCCTCG	CGAGGCCGTAGGTTGCGCC
1164	GCGCAACCTACGGCCTCGG	CCGAGGCCGTAGGTTGCGC
1165	CGCAACCTACGGCCTCGGC	GCCGAGGCCGTAGGTTGCG
1166	GCAACCTACGGCCTCGGCC	GGCCGAGGCCGTAGGTTGC
1167	CAACCTACGGCCTCGGCCC	GGGCCGAGGCCGTAGGTTG
1168	AACCTACGGCCTCGGCCCA	TGGGCCGAGGCCGTAGGTT
1169	ACCTACGGCCTCGGCCCAG	CTGGGCCGAGGCCGTAGGT
1170	CCTACGGCCTCGGCCCAGA	TCTGGGCCGAGGCCGTAGG
1171	CTACGGCCTCGGCCCAGAA	TTCTGGGCCGAGGCCGTAG
1172	TACGGCCTCGGCCCAGAAG	CTTCTGGGCCGAGGCCGTA
1173	ACGGCCTCGGCCCAGAAGC	GCTTCTGGGCCGAGGCCGT
1174	CGGCCTCGGCCCAGAAGCT	AGCTTCTGGGCCGAGGCCG
1175	GGCCTCGGCCCAGAAGCTG	CAGCTTCTGGGCCGAGGCC
1176	GCCTCGGCCCAGAAGCTGG	CCAGCTTCTGGGCCGAGGC
1177	CCTCGGCCCAGAAGCTGGT	ACCAGCTTCTGGGCCGAGG
1178	CTCGGCCCAGAAGCTGGTG	CACCAGCTTCTGGGCCGAG
1179	TCGGCCCAGAAGCTGGTGC	GCACCAGCTTCTGGGCCGA
1180	CGGCCCAGAAGCTGGTGCG	CGCACCAGCTTCTGGGCCG
1181	GGCCCAGAAGCTGGTGCGG	CCGCACCAGCTTCTGGGCC
1182	GCCCAGAAGCTGGTGCGGC	GCCGCACCAGCTTCTGGGC
1183	CCCAGAAGCTGGTGCGGCC	GGCCGCACCAGCTTCTGGG
1184	CCAGAAGCTGGTGCGGCCG	CGGCCGCACCAGCTTCTGG
1185	CAGAAGCTGGTGCGGCCGA	TCGGCCGCACCAGCTTCTG
1186	AGAAGCTGGTGCGGCCGAT	ATCGGCCGCACCAGCTTCT
1187	GAAGCTGGTGCGGCCGATC	GATCGGCCGCACCAGCTTC
1188	AAGCTGGTGCGGCCGATCC	GGATCGGCCGCACCAGCTT
1189	AGCTGGTGCGGCCGATCCG	CGGATCGGCCGCACCAGCT
1190	GCTGGTGCGGCCGATCCGC	GCGGATCGGCCGCACCAGC
1191	CTGGTGCGGCCGATCCGCG	CGCGGATCGGCCGCACCAG
1192	TGGTGCGGCCGATCCGCGC	GCGCGGATCGGCCGCACCA
1193	GGTGCGGCCGATCCGCGCC	GGCGCGGATCGGCCGCACC
1194	GTGCGGCCGATCCGCGCCG	CGGCGCGGATCGGCCGCAC
1195	TGCGGCCGATCCGCGCCGT	ACGGCGCGGATCGGCCGCA
1196	GCGGCCGATCCGCGCCGTG	CACGGCGCGGATCGGCCGC
1197	CGGCCGATCCGCGCCGTGT	ACACGGCGCGGATCGGCCG
1198	GGCCGATCCGCGCCGTGTG	CACACGGCGCGGATCGGCC
1199	GCCGATCCGCGCCGTGTGC	GCACACGGCGCGGATCGGC
1200	CCGATCCGCGCCGTGTGCC	GGCACACGGCGCGGATCGG
1201	CGATCCGCGCCGTGTGCCG	CGGCACACGGCGCGGATCG
1202	GATCCGCGCCGTGTGCCGC	GCGGCACACGGCGCGGATC
1203	ATCCGCGCCGTGTGCCGCA	TGCGGCACACGGCGCGGAT
1204	TCCGCGCCGTGTGCCGCAT	ATGCGGCACACGGCGCGGA
1205	CCGCGCCGTGTGCCGCATC	GATGCGGCACACGGCGCGG
1206	CGCGCCGTGTGCCGCATCC	GGATGCGGCACACGGCGCG
1207	GCGCCGTGTGCCGCATCCT	AGGATGCGGCACACGGCGC
1208	CGCCGTGTGCCGCATCCTG	CAGGATGCGGCACACGGCG
1209	GCCGTGTGCCGCATCCTGC	GCAGGATGCGGCACACGGC
1210	CCGTGTGCCGCATCCTGCA	TGCAGGATGCGGCACACGG
1211	CGTGTGCCGCATCCTGCAG	CTGCAGGATGCGGCACACG
1212	GTGTGCCGCATCCTGCAGA	TCTGCAGGATGCGGCACAC
1213	TGTGCCGCATCCTGCAGAT	ATCTGCAGGATGCGGCACA
1214	GTGCCGCATCCTGCAGATC	GATCTGCAGGATGCGGCAC
1215	TGCCGCATCCTGCAGATCC	GGATCTGCAGGATGCGGCA
1216	GCCGCATCCTGCAGATCCC	GGGATCTGCAGGATGCGGC
1217	CCGCATCCTGCAGATCCCG	CGGGATCTGCAGGATGCGG
1218	CGCATCCTGCAGATCCCGG	CCGGGATCTGCAGGATGCG
1219	GCATCCTGCAGATCCCGGA	TCCGGGATCTGCAGGATGC
1220	CATCCTGCAGATCCCGGAG	CTCCGGGATCTGCAGGATG
1221	ATCCTGCAGATCCCGGAGT	ACTCCGGGATCTGCAGGAT
1222	TCCTGCAGATCCCGGAGTC	GACTCCGGGATCTGCAGGA
1223	CCTGCAGATCCCGGAGTCC	GGACTCCGGGATCTGCAGG
1224	CTGCAGATCCCGGAGTCCG	CGGACTCCGGGATCTGCAG
1225	TGCAGATCCCGGAGTCCGA	TCGGACTCCGGGATCTGCA
1226	GCAGATCCCGGAGTCCGAC	GTCGGACTCCGGGATCTGC
1227	CAGATCCCGGAGTCCGACC	GGTCGGACTCCGGGATCTG
1228	AGATCCCGGAGTCCGACCC	GGGTCGGACTCCGGGATCT
1229	GATCCCGGAGTCCGACCCC	GGGGTCGGACTCCGGGATC
1230	ATCCCGGAGTCCGACCCCT	AGGGGTCGGACTCCGGGAT
1231	TCCCGGAGTCCGACCCCTC	GAGGGGTCGGACTCCGGGA
1232	CCCGGAGTCCGACCCCTCC	GGAGGGGTCGGACTCCGGG
1233	CCGGAGTCCGACCCCTCCA	TGGAGGGGTCGGACTCCGG
1234	CGGAGTCCGACCCCTCCAA	TTGGAGGGGTCGGACTCCG
1235	GGAGTCCGACCCCTCCAAC	GTTGGAGGGGTCGGACTCC
1236	GAGTCCGACCCCTCCAACC	GGTTGGAGGGGTCGGACTC
1237	AGTCCGACCCCTCCAACCT	AGGTTGGAGGGGTCGGACT
1238	GTCCGACCCCTCCAACCTG	CAGGTTGGAGGGGTCGGAC
1239	TCCGACCCCTCCAACCTGC	GCAGGTTGGAGGGGTCGGA
1240	CCGACCCCTCCAACCTGCG	CGCAGGTTGGAGGGGTCGG
1241	CGACCCCTCCAACCTGCGG	CCGCAGGTTGGAGGGGTCG
1242	GACCCCTCCAACCTGCGGC	GCCGCAGGTTGGAGGGGTC
1243	ACCCCTCCAACCTGCGGCC	GGCCGCAGGTTGGAGGGGT
1244	CCCCTCCAACCTGCGGCCC	GGGCCGCAGGTTGGAGGGG
1245	CCCTCCAACCTGCGGCCCT	AGGGCCGCAGGTTGGAGGG
1246	CCTCCAACCTGCGGCCCTA	TAGGGCCGCAGGTTGGAGG
1247	CTCCAACCTGCGGCCCTAG	CTAGGGCCGCAGGTTGGAG
1248	TCCAACCTGCGGCCCTAGA	TCTAGGGCCGCAGGTTGGA
1249	CCAACCTGCGGCCCTAGAG	CTCTAGGGCCGCAGGTTGG
1250	CAACCTGCGGCCCTAGAGC	GCTCTAGGGCCGCAGGTTG
1251	AACCTGCGGCCCTAGAGCG	CGCTCTAGGGCCGCAGGTT
1252	ACCTGCGGCCCTAGAGCGC	GCGCTCTAGGGCCGCAGGT
1253	CCTGCGGCCCTAGAGCGCC	GGCGCTCTAGGGCCGCAGG
1254	CTGCGGCCCTAGAGCGCCC	GGGCGCTCTAGGGCCGCAG
1255	TGCGGCCCTAGAGCGCCCC	GGGGCGCTCTAGGGCCGCA
1256	GCGGCCCTAGAGCGCCCCC	GGGGGCGCTCTAGGGCCGC
1257	CGGCCCTAGAGCGCCCCCG	CGGGGGCGCTCTAGGGCCG
1258	GGCCCTAGAGCGCCCCCGC	GCGGGGGCGCTCTAGGGCC
1259	GCCCTAGAGCGCCCCCGCC	GGCGGGGGCGCTCTAGGGC
1260	CCCTAGAGCGCCCCCGCCG	CGGCGGGGGCGCTCTAGGG
1261	CCTAGAGCGCCCCCGCCGC	GCGGCGGGGGCGCTCTAGG
1262	CTAGAGCGCCCCCGCCGCC	GGCGGCGGGGGCGCTCTAG
1263	TAGAGCGCCCCCGCCGCCC	GGGCGGCGGGGGCGCTCTA
1264	AGAGCGCCCCCGCCGCCCC	GGGGCGGCGGGGGCGCTCT
1265	GAGCGCCCCCGCCGCCCCG	CGGGGCGGCGGGGGCGCTC
1266	AGCGCCCCCGCCGCCCCGG	CCGGGGCGGCGGGGGCGCT
1267	GCGCCCCCGCCGCCCCGGG	CCCGGGGCGGCGGGGGCGC
1268	CGCCCCCGCCGCCCCGGGG	CCCCGGGGCGGCGGGGGCG
1269	GCCCCCGCCGCCCCGGGGG	CCCCCGGGGCGGCGGGGGC
1270	CCCCCGCCGCCCCGGGGGA	TCCCCCGGGGCGGCGGGGG
1271	CCCCGCCGCCCCGGGGGAA	TTCCCCCGGGGCGGCGGGG
1272	CCCGCCGCCCCGGGGGAAG	CTTCCCCCGGGGCGGCGGG
1273	CCGCCGCCCCGGGGGAAGG	CCTTCCCCCGGGGCGGCGG
1274	CGCCGCCCCGGGGGAAGGA	TCCTTCCCCCGGGGCGGCG
1275	GCCGCCCCGGGGGAAGGAG	CTCCTTCCCCCGGGGCGGC
1276	CCGCCCCGGGGGAAGGAGA	TCTCCTTCCCCCGGGGCGG
1277	CGCCCCGGGGGAAGGAGAG	CTCTCCTTCCCCCGGGGCG
1278	GCCCCGGGGGAAGGAGAGC	GCTCTCCTTCCCCCGGGGC
1279	CCCCGGGGGAAGGAGAGCG	CGCTCTCCTTCCCCCGGGG
1280	CCCGGGGGAAGGAGAGCGC	GCGCTCTCCTTCCCCCGGG
1281	CCGGGGGAAGGAGAGCGCG	CGCGCTCTCCTTCCCCCGG
1282	CGGGGGAAGGAGAGCGCGA	TCGCGCTCTCCTTCCCCCG
1283	GGGGGAAGGAGAGCGCGAG	CTCGCGCTCTCCTTCCCCC
1284	GGGGAAGGAGAGCGCGAGC	GCTCGCGCTCTCCTTCCCC
1285	GGGAAGGAGAGCGCGAGCG	CGCTCGCGCTCTCCTTCCC
1286	GGAAGGAGAGCGCGAGCGC	GCGCTCGCGCTCTCCTTCC
1287	GAAGGAGAGCGCGAGCGCG	CGCGCTCGCGCTCTCCTTC
1288	AAGGAGAGCGCGAGCGCGC	GCGCGCTCGCGCTCTCCTT
1289	AGGAGAGCGCGAGCGCGCT	AGCGCGCTCGCGCTCTCCT
1290	GGAGAGCGCGAGCGCGCTG	CAGCGCGCTCGCGCTCTCC
1291	GAGAGCGCGAGCGCGCTGA	TCAGCGCGCTCGCGCTCTC
1292	AGAGCGCGAGCGCGCTGAG	CTCAGCGCGCTCGCGCTCT
1293	GAGCGCGAGCGCGCTGAGC	GCTCAGCGCGCTCGCGCTC
1294	AGCGCGAGCGCGCTGAGCA	TGCTCAGCGCGCTCGCGCT
1295	GCGCGAGCGCGCTGAGCAG	CTGCTCAGCGCGCTCGCGC
1296	CGCGAGCGCGCTGAGCAGA	TCTGCTCAGCGCGCTCGCG
1297	GCGAGCGCGCTGAGCAGAC	GTCTGCTCAGCGCGCTCGC
1298	CGAGCGCGCTGAGCAGACA	TGTCTGCTCAGCGCGCTCG
1299	GAGCGCGCTGAGCAGACAG	CTGTCTGCTCAGCGCGCTC
1300	AGCGCGCTGAGCAGACAGA	TCTGTCTGCTCAGCGCGCT
1301	GCGCGCTGAGCAGACAGAG	CTCTGTCTGCTCAGCGCGC
1302	CGCGCTGAGCAGACAGAGC	GCTCTGTCTGCTCAGCGCG
1303	GCGCTGAGCAGACAGAGCG	CGCTCTGTCTGCTCAGCGC
1304	CGCTGAGCAGACAGAGCGG	CCGCTCTGTCTGCTCAGCG
1305	GCTGAGCAGACAGAGCGGG	CCCGCTCTGTCTGCTCAGC
1306	CTGAGCAGACAGAGCGGGA	TCCCGCTCTGTCTGCTCAG
1307	TGAGCAGACAGAGCGGGAG	CTCCCGCTCTGTCTGCTCA
1308	GAGCAGACAGAGCGGGAGA	TCTCCCGCTCTGTCTGCTC
1309	AGCAGACAGAGCGGGAGAA	TTCTCCCGCTCTGTCTGCT
1310	GCAGACAGAGCGGGAGAAC	GTTCTCCCGCTCTGTCTGC
1311	CAGACAGAGCGGGAGAACG	CGTTCTCCCGCTCTGTCTG
1312	AGACAGAGCGGGAGAACGC	GCGTTCTCCCGCTCTGTCT
1313	GACAGAGCGGGAGAACGCG	CGCGTTCTCCCGCTCTGTC
1314	ACAGAGCGGGAGAACGCGT	ACGCGTTCTCCCGCTCTGT
1315	CAGAGCGGGAGAACGCGTC	GACGCGTTCTCCCGCTCTG
1316	AGAGCGGGAGAACGCGTCC	GGACGCGTTCTCCCGCTCT
1317	GAGCGGGAGAACGCGTCCT	AGGACGCGTTCTCCCGCTC
1318	AGCGGGAGAACGCGTCCTC	GAGGACGCGTTCTCCCGCT
1319	GCGGGAGAACGCGTCCTCG	CGAGGACGCGTTCTCCCGC
1320	CGGGAGAACGCGTCCTCGC	GCGAGGACGCGTTCTCCCG
1321	GGGAGAACGCGTCCTCGCC	GGCGAGGACGCGTTCTCCC
1322	GGAGAACGCGTCCTCGCCC	GGGCGAGGACGCGTTCTCC
1323	GAGAACGCGTCCTCGCCCG	CGGGCGAGGACGCGTTCTC
1324	AGAACGCGTCCTCGCCCGC	GCGGGCGAGGACGCGTTCT
1325	GAACGCGTCCTCGCCCGCC	GGCGGGCGAGGACGCGTTC
1326	AACGCGTCCTCGCCCGCCG	CGGCGGGCGAGGACGCGTT
1327	ACGCGTCCTCGCCCGCCGG	CCGGCGGGCGAGGACGCGT
1328	CGCGTCCTCGCCCGCCGGC	GCCGGCGGGCGAGGACGCG
1329	GCGTCCTCGCCCGCCGGCC	GGCCGGCGGGCGAGGACGC
1330	CGTCCTCGCCCGCCGGCCG	CGGCCGGCGGGCGAGGACG
1331	GTCCTCGCCCGCCGGCCGG	CCGGCCGGCGGGCGAGGAC
1332	TCCTCGCCCGCCGGCCGGG	CCCGGCCGGCGGGCGAGGA
1333	CCTCGCCCGCCGGCCGGGA	TCCCGGCCGGCGGGCGAGG
1334	CTCGCCCGCCGGCCGGGAG	CTCCCGGCCGGCGGGCGAG
1335	TCGCCCGCCGGCCGGGAGG	CCTCCCGGCCGGCGGGCGA
1336	CGCCCGCCGGCCGGGAGGC	GCCTCCCGGCCGGCGGGCG
1337	GCCCGCCGGCCGGGAGGCC	GGCCTCCCGGCCGGCGGGC
1338	CCCGCCGGCCGGGAGGCCC	GGGCCTCCCGGCCGGCGGG
1339	CCGCCGGCCGGGAGGCCCC	GGGGCCTCCCGGCCGGCGG
1340	CGCCGGCCGGGAGGCCCCG	CGGGGCCTCCCGGCCGGCG
1341	GCCGGCCGGGAGGCCCCGG	CCGGGGCCTCCCGGCCGGC
1342	CCGGCCGGGAGGCCCCGGA	TCCGGGGCCTCCCGGCCGG
1343	CGGCCGGGAGGCCCCGGAG	CTCCGGGGCCTCCCGGCCG
1344	GGCCGGGAGGCCCCGGAGC	GCTCCGGGGCCTCCCGGCC
1345	GCCGGGAGGCCCCGGAGCT	AGCTCCGGGGCCTCCCGGC
1346	CCGGGAGGCCCCGGAGCTG	CAGCTCCGGGGCCTCCCGG
1347	CGGGAGGCCCCGGAGCTGG	CCAGCTCCGGGGCCTCCCG
1348	GGGAGGCCCCGGAGCTGGC	GCCAGCTCCGGGGCCTCCC
1349	GGAGGCCCCGGAGCTGGCC	GGCCAGCTCCGGGGCCTCC
1350	GAGGCCCCGGAGCTGGCCC	GGGCCAGCTCCGGGGCCTC
1351	AGGCCCCGGAGCTGGCCCA	TGGGCCAGCTCCGGGGCCT
1352	GGCCCCGGAGCTGGCCCAT	ATGGGCCAGCTCCGGGGCC
1353	GCCCCGGAGCTGGCCCATG	CATGGGCCAGCTCCGGGGC
1354	CCCCGGAGCTGGCCCATGG	CCATGGGCCAGCTCCGGGG
1355	CCCGGAGCTGGCCCATGGG	CCCATGGGCCAGCTCCGGG
1356	CCGGAGCTGGCCCATGGGG	CCCCATGGGCCAGCTCCGG
1357	CGGAGCTGGCCCATGGGGA	TCCCCATGGGCCAGCTCCG
1358	GGAGCTGGCCCATGGGGAG	CTCCCCATGGGCCAGCTCC
1359	GAGCTGGCCCATGGGGAGC	GCTCCCCATGGGCCAGCTC
1360	AGCTGGCCCATGGGGAGCA	TGCTCCCCATGGGCCAGCT
1361	GCTGGCCCATGGGGAGCAG	CTGCTCCCCATGGGCCAGC
1362	CTGGCCCATGGGGAGCAGG	CCTGCTCCCCATGGGCCAG
1363	TGGCCCATGGGGAGCAGGC	GCCTGCTCCCCATGGGCCA
1364	GGCCCATGGGGAGCAGGCG	CGCCTGCTCCCCATGGGCC
1365	GCCCATGGGGAGCAGGCGC	GCGCCTGCTCCCCATGGGC
1366	CCCATGGGGAGCAGGCGCC	GGCGCCTGCTCCCCATGGG
1367	CCATGGGGAGCAGGCGCCC	GGGCGCCTGCTCCCCATGG
1368	CATGGGGAGCAGGCGCCCG	CGGGCGCCTGCTCCCCATG
1369	ATGGGGAGCAGGCGCCCGG	CCGGGCGCCTGCTCCCCAT
1370	TGGGGAGCAGGCGCCCGGT	ACCGGGCGCCTGCTCCCCA
1371	GGGGAGCAGGCGCCCGGTG	CACCGGGCGCCTGCTCCCC
1372	GGGAGCAGGCGCCCGGTGC	GCACCGGGCGCCTGCTCCC
1373	GGAGCAGGCGCCCGGTGCC	GGCACCGGGCGCCTGCTCC
1374	GAGCAGGCGCCCGGTGCCG	CGGCACCGGGCGCCTGCTC
1375	AGCAGGCGCCCGGTGCCGG	CCGGCACCGGGCGCCTGCT
1376	GCAGGCGCCCGGTGCCGGC	GCCGGCACCGGGCGCCTGC
1377	CAGGCGCCCGGTGCCGGCC	GGCCGGCACCGGGCGCCTG
1378	AGGCGCCCGGTGCCGGCCA	TGGCCGGCACCGGGCGCCT
1379	GGCGCCCGGTGCCGGCCAC	GTGGCCGGCACCGGGCGCC
1380	GCGCCCGGTGCCGGCCACG	CGTGGCCGGCACCGGGCGC
1381	CGCCCGGTGCCGGCCACGA	TCGTGGCCGGCACCGGGCG
1382	GCCCGGTGCCGGCCACGAC	GTCGTGGCCGGCACCGGGC
1383	CCCGGTGCCGGCCACGACG	CGTCGTGGCCGGCACCGGG
1384	CCGGTGCCGGCCACGACGA	TCGTCGTGGCCGGCACCGG
1385	CGGTGCCGGCCACGACGAC	GTCGTCGTGGCCGGCACCG
1386	GGTGCCGGCCACGACGACC	GGTCGTCGTGGCCGGCACC
1387	GTGCCGGCCACGACGACCG	CGGTCGTCGTGGCCGGCAC
1388	TGCCGGCCACGACGACCGC	GCGGTCGTCGTGGCCGGCA
1389	GCCGGCCACGACGACCGCC	GGCGGTCGTCGTGGCCGGC
1390	CCGGCCACGACGACCGCCA	TGGCGGTCGTCGTGGCCGG
1391	CGGCCACGACGACCGCCAC	GTGGCGGTCGTCGTGGCCG
1392	GGCCACGACGACCGCCACC	GGTGGCGGTCGTCGTGGCC
1393	GCCACGACGACCGCCACCG	CGGTGGCGGTCGTCGTGGC
1394	CCACGACGACCGCCACCGC	GCGGTGGCGGTCGTCGTGG
1395	CACGACGACCGCCACCGCC	GGCGGTGGCGGTCGTCGTG
1396	ACGACGACCGCCACCGCCC	GGGCGGTGGCGGTCGTCGT
1397	CGACGACCGCCACCGCCCG	CGGGCGGTGGCGGTCGTCG
1398	GACGACCGCCACCGCCCGC	GCGGGCGGTGGCGGTCGTC
1399	ACGACCGCCACCGCCCGCG	CGCGGGCGGTGGCGGTCGT
1400	CGACCGCCACCGCCCGCGC	GCGCGGGCGGTGGCGGTCG
1401	GACCGCCACCGCCCGCGCC	GGCGCGGGCGGTGGCGGTC
1402	ACCGCCACCGCCCGCGCCG	CGGCGCGGGCGGTGGCGGT
1403	CCGCCACCGCCCGCGCCGC	GCGGCGCGGGCGGTGGCGG
1404	CGCCACCGCCCGCGCCGCG	CGCGGCGCGGGCGGTGGCG
1405	GCCACCGCCCGCGCCGCGA	TCGCGGCGCGGGCGGTGGC
1406	CCACCGCCCGCGCCGCGAC	GTCGCGGCGCGGGCGGTGG
1407	CACCGCCCGCGCCGCGACC	GGTCGCGGCGCGGGCGGTG
1408	ACCGCCCGCGCCGCGACCG	CGGTCGCGGCGCGGGCGGT
1409	CCGCCCGCGCCGCGACCGG	CCGGTCGCGGCGCGGGCGG
1410	CGCCCGCGCCGCGACCGGC	GCCGGTCGCGGCGCGGGCG
1411	GCCCGCGCCGCGACCGGCC	GGCCGGTCGCGGCGCGGGC
1412	CCCGCGCCGCGACCGGCCG	CGGCCGGTCGCGGCGCGGG
1413	CCGCGCCGCGACCGGCCGG	CCGGCCGGTCGCGGCGCGG
1414	CGCGCCGCGACCGGCCGGT	ACCGGCCGGTCGCGGCGCG
1415	GCGCCGCGACCGGCCGGTG	CACCGGCCGGTCGCGGCGC
1416	CGCCGCGACCGGCCGGTGA	TCACCGGCCGGTCGCGGCG
1417	GCCGCGACCGGCCGGTGAA	TTCACCGGCCGGTCGCGGC
1418	CCGCGACCGGCCGGTGAAG	CTTCACCGGCCGGTCGCGG
1419	CGCGACCGGCCGGTGAAGC	GCTTCACCGGCCGGTCGCG
1420	GCGACCGGCCGGTGAAGCC	GGCTTCACCGGCCGGTCGC
1421	CGACCGGCCGGTGAAGCCC	GGGCTTCACCGGCCGGTCG
1422	GACCGGCCGGTGAAGCCCA	TGGGCTTCACCGGCCGGTC
1423	ACCGGCCGGTGAAGCCCAG	CTGGGCTTCACCGGCCGGT
1424	CCGGCCGGTGAAGCCCAGG	CCTGGGCTTCACCGGCCGG
1425	CGGCCGGTGAAGCCCAGGG	CCCTGGGCTTCACCGGCCG
1426	GGCCGGTGAAGCCCAGGGA	TCCCTGGGCTTCACCGGCC
1427	GCCGGTGAAGCCCAGGGAC	GTCCCTGGGCTTCACCGGC
1428	CCGGTGAAGCCCAGGGACC	GGTCCCTGGGCTTCACCGG
1429	CGGTGAAGCCCAGGGACCC	GGGTCCCTGGGCTTCACCG
1430	GGTGAAGCCCAGGGACCCC	GGGGTCCCTGGGCTTCACC
1431	GTGAAGCCCAGGGACCCCC	GGGGGTCCCTGGGCTTCAC
1432	TGAAGCCCAGGGACCCCCC	GGGGGGTCCCTGGGCTTCA
1433	GAAGCCCAGGGACCCCCCT	AGGGGGGTCCCTGGGCTTC
1434	AAGCCCAGGGACCCCCCTC	GAGGGGGGTCCCTGGGCTT
1435	AGCCCAGGGACCCCCCTCT	AGAGGGGGGTCCCTGGGCT
1436	GCCCAGGGACCCCCCTCTG	CAGAGGGGGGTCCCTGGGC
1437	CCCAGGGACCCCCCTCTGG	CCAGAGGGGGGTCCCTGGG
1438	CCAGGGACCCCCCTCTGGG	CCCAGAGGGGGGTCCCTGG
1439	CAGGGACCCCCCTCTGGGA	TCCCAGAGGGGGGTCCCTG
1440	AGGGACCCCCCTCTGGGAG	CTCCCAGAGGGGGGTCCCT
1441	GGGACCCCCCTCTGGGAGA	TCTCCCAGAGGGGGGTCCC
1442	GGACCCCCCTCTGGGAGAG	CTCTCCCAGAGGGGGGTCC
1443	GACCCCCCTCTGGGAGAGC	GCTCTCCCAGAGGGGGGTC
1444	ACCCCCCTCTGGGAGAGCC	GGCTCTCCCAGAGGGGGGT
1445	CCCCCCTCTGGGAGAGCCC	GGGCTCTCCCAGAGGGGGG
1446	CCCCCTCTGGGAGAGCCCC	GGGGCTCTCCCAGAGGGGG
1447	CCCCTCTGGGAGAGCCCCA	TGGGGCTCTCCCAGAGGGG
1448	CCCTCTGGGAGAGCCCCAT	ATGGGGCTCTCCCAGAGGG
1449	CCTCTGGGAGAGCCCCATG	CATGGGGCTCTCCCAGAGG
1450	CTCTGGGAGAGCCCCATGA	TCATGGGGCTCTCCCAGAG
1451	TCTGGGAGAGCCCCATGAG	CTCATGGGGCTCTCCCAGA
1452	CTGGGAGAGCCCCATGAGG	CCTCATGGGGCTCTCCCAG
1453	TGGGAGAGCCCCATGAGGG	CCCTCATGGGGCTCTCCCA
1454	GGGAGAGCCCCATGAGGGC	GCCCTCATGGGGCTCTCCC
1455	GGAGAGCCCCATGAGGGCA	TGCCCTCATGGGGCTCTCC
1456	GAGAGCCCCATGAGGGCAG	CTGCCCTCATGGGGCTCTC
1457	AGAGCCCCATGAGGGCAGG	CCTGCCCTCATGGGGCTCT
1458	GAGCCCCATGAGGGCAGGA	TCCTGCCCTCATGGGGCTC
1459	AGCCCCATGAGGGCAGGAG	CTCCTGCCCTCATGGGGCT
1460	GCCCCATGAGGGCAGGAGA	TCTCCTGCCCTCATGGGGC
1461	CCCCATGAGGGCAGGAGAG	CTCTCCTGCCCTCATGGGG
1462	CCCATGAGGGCAGGAGAGT	ACTCTCCTGCCCTCATGGG
1463	CCATGAGGGCAGGAGAGTG	CACTCTCCTGCCCTCATGG
1464	CATGAGGGCAGGAGAGTGA	TCACTCTCCTGCCCTCATG
1465	ATGAGGGCAGGAGAGTGAT	ATCACTCTCCTGCCCTCAT
1466	TGAGGGCAGGAGAGTGATG	CATCACTCTCCTGCCCTCA
1467	GAGGGCAGGAGAGTGATGG	CCATCACTCTCCTGCCCTC
1468	AGGGCAGGAGAGTGATGGA	TCCATCACTCTCCTGCCCT
1469	GGGCAGGAGAGTGATGGAG	CTCCATCACTCTCCTGCCC
1470	GGCAGGAGAGTGATGGAGA	TCTCCATCACTCTCCTGCC
1471	GCAGGAGAGTGATGGAGAG	CTCTCCATCACTCTCCTGC
1472	CAGGAGAGTGATGGAGAGT	ACTCTCCATCACTCTCCTG
1473	AGGAGAGTGATGGAGAGTA	TACTCTCCATCACTCTCCT
1474	GGAGAGTGATGGAGAGTAC	GTACTCTCCATCACTCTCC
1475	GAGAGTGATGGAGAGTACG	CGTACTCTCCATCACTCTC
1476	AGAGTGATGGAGAGTACGC	GCGTACTCTCCATCACTCT
1477	GAGTGATGGAGAGTACGCC	GGCGTACTCTCCATCACTC
1478	AGTGATGGAGAGTACGCCC	GGGCGTACTCTCCATCACT
1479	GTGATGGAGAGTACGCCCA	TGGGCGTACTCTCCATCAC
1480	TGATGGAGAGTACGCCCAG	CTGGGCGTACTCTCCATCA
1481	GATGGAGAGTACGCCCAGC	GCTGGGCGTACTCTCCATC
1482	ATGGAGAGTACGCCCAGCT	AGCTGGGCGTACTCTCCAT
1483	TGGAGAGTACGCCCAGCTT	AAGCTGGGCGTACTCTCCA
1484	GGAGAGTACGCCCAGCTTC	GAAGCTGGGCGTACTCTCC
1485	GAGAGTACGCCCAGCTTCC	GGAAGCTGGGCGTACTCTC
1486	AGAGTACGCCCAGCTTCCT	AGGAAGCTGGGCGTACTCT
1487	GAGTACGCCCAGCTTCCTG	CAGGAAGCTGGGCGTACTC
1488	AGTACGCCCAGCTTCCTGA	TCAGGAAGCTGGGCGTACT
1489	GTACGCCCAGCTTCCTGAA	TTCAGGAAGCTGGGCGTAC
1490	TACGCCCAGCTTCCTGAAG	CTTCAGGAAGCTGGGCGTA
1491	ACGCCCAGCTTCCTGAAGG	CCTTCAGGAAGCTGGGCGT
1492	CGCCCAGCTTCCTGAAGGG	CCCTTCAGGAAGCTGGGCG
1493	GCCCAGCTTCCTGAAGGGC	GCCCTTCAGGAAGCTGGGC
1494	CCCAGCTTCCTGAAGGGCA	TGCCCTTCAGGAAGCTGGG
1495	CCAGCTTCCTGAAGGGCAC	GTGCCCTTCAGGAAGCTGG
1496	CAGCTTCCTGAAGGGCACC	GGTGCCCTTCAGGAAGCTG
1497	AGCTTCCTGAAGGGCACCC	GGGTGCCCTTCAGGAAGCT
1498	GCTTCCTGAAGGGCACCCC	GGGGTGCCCTTCAGGAAGC
1499	CTTCCTGAAGGGCACCCCA	TGGGGTGCCCTTCAGGAAG
1500	TTCCTGAAGGGCACCCCAA	TTGGGGTGCCCTTCAGGAA
1501	TCCTGAAGGGCACCCCAAC	GTTGGGGTGCCCTTCAGGA
1502	CCTGAAGGGCACCCCAACC	GGTTGGGGTGCCCTTCAGG
1503	CTGAAGGGCACCCCAACCT	AGGTTGGGGTGCCCTTCAG
1504	TGAAGGGCACCCCAACCTG	CAGGTTGGGGTGCCCTTCA
1505	GAAGGGCACCCCAACCTGG	CCAGGTTGGGGTGCCCTTC
1506	AAGGGCACCCCAACCTGGG	CCCAGGTTGGGGTGCCCTT
1507	AGGGCACCCCAACCTGGGA	TCCCAGGTTGGGGTGCCCT
1508	GGGCACCCCAACCTGGGAG	CTCCCAGGTTGGGGTGCCC
1509	GGCACCCCAACCTGGGAGA	TCTCCCAGGTTGGGGTGCC
1510	GCACCCCAACCTGGGAGAA	TTCTCCCAGGTTGGGGTGC
1511	CACCCCAACCTGGGAGAAG	CTTCTCCCAGGTTGGGGTG
1512	ACCCCAACCTGGGAGAAGA	TCTTCTCCCAGGTTGGGGT
1513	CCCCAACCTGGGAGAAGAC	GTCTTCTCCCAGGTTGGGG
1514	CCCAACCTGGGAGAAGACG	CGTCTTCTCCCAGGTTGGG
1515	CCAACCTGGGAGAAGACGG	CCGTCTTCTCCCAGGTTGG
1516	CAACCTGGGAGAAGACGGC	GCCGTCTTCTCCCAGGTTG
1517	AACCTGGGAGAAGACGGCC	GGCCGTCTTCTCCCAGGTT
1518	ACCTGGGAGAAGACGGCCC	GGGCCGTCTTCTCCCAGGT
1519	CCTGGGAGAAGACGGCCCC	GGGGCCGTCTTCTCCCAGG
1520	CTGGGAGAAGACGGCCCCA	TGGGGCCGTCTTCTCCCAG
1521	TGGGAGAAGACGGCCCCAG	CTGGGGCCGTCTTCTCCCA
1522	GGGAGAAGACGGCCCCAGA	TCTGGGGCCGTCTTCTCCC
1523	GGAGAAGACGGCCCCAGAG	CTCTGGGGCCGTCTTCTCC
1524	GAGAAGACGGGGCCAGAGA	TCTCTGGGGCCGTCTTCTC
1525	AGAAGACGGCCCCAGAGAA	TTCTCTGGGGCCGTCTTCT
1526	GAAGACGGCCCCAGAGAAC	GTTCTCTGGGGCCGTCTTC
1527	AAGACGGCCCCAGAGAACG	CGTTCTCTGGGGCCGTCTT
1528	AGACGGCCCCAGAGAACGG	CCGTTCTCTGGGGCCGTCT
1529	GACGGCCCCAGAGAACGGC	GCCGTTCTCTGGGGCCGTC
1530	ACGGCCCCAGAGAACGGCA	TGCCGTTCTCTGGGGCCGT
1531	CGGCCCCAGAGAACGGCAT	ATGCCGTTCTCTGGGGCCG
1532	GGCCCCAGAGAACGGCATC	GATGCCGTTCTCTGGGGCC
1533	GCCCCAGAGAACGGCATCG	CGATGCCGTTCTCTGGGGC
1534	CCCCAGAGAACGGCATCGT	ACGATGCCGTTCTCTGGGG
1535	CCCAGAGAACGGCATCGTG	CACGATGCCGTTCTCTGGG
1536	CCAGAGAACGGCATCGTGA	TCACGATGCCGTTCTCTGG
1537	CAGAGAACGGCATCGTGAG	CTCACGATGCCGTTCTCTG
1538	AGAGAACGGCATCGTGAGA	TCTCACGATGCCGTTCTCT
1539	GAGAACGGCATCGTGAGAC	GTCTCACGATGCCGTTCTC
1540	AGAACGGCATCGTGAGACA	TGTCTCACGATGCCGTTCT
1541	GAACGGCATCGTGAGACAG	CTGTCTCACGATGCCGTTC
1542	AACGGCATCGTGAGACAGG	CCTGTCTCACGATGCCGTT
1543	ACGGCATCGTGAGACAGGA	TCCTGTCTCACGATGCCGT
1544	CGGCATCGTGAGACAGGAG	CTCCTGTCTCACGATGCCG
1545	GGCATCGTGAGACAGGAGC	GCTCCTGTCTCACGATGCC
1546	GCATCGTGAGACAGGAGCC	GGCTCCTGTCTCACGATGC
1547	CATCGTGAGACAGGAGCCC	GGGCTCCTGTCTCACGATG
1548	ATCGTGAGACAGGAGCCCG	CGGGCTCCTGTCTCACGAT
1549	TCGTGAGACAGGAGCCCGG	CCGGGCTCCTGTCTCACGA
1550	CGTGAGACAGGAGCCCGGC	GCCGGGCTCCTGTCTCACG
1551	GTGAGACAGGAGCCCGGCA	TGCCGGGCTCCTGTCTCAC
1552	TGAGACAGGAGCCCGGCAG	CTGCCGGGCTCCTGTCTCA
1553	GAGACAGGAGCCCGGCAGC	GCTGCCGGGCTCCTGTCTC
1554	AGACAGGAGCCCGGCAGCC	GGCTGCCGGGCTCCTGTCT
1555	GACAGGAGCCCGGCAGCCC	GGGCTGCCGGGCTCCTGTC
1556	ACAGGAGCCCGGCAGCCCG	CGGGCTGCCGGGCTCCTGT
1557	CAGGAGCCCGGCAGCCCGC	GCGGGCTGCCGGGCTCCTG
1558	AGGAGCCCGGCAGCCCGCC	GGCGGGCTGCCGGGCTCCT
1559	GGAGCCCGGCAGCCCGCCT	AGGCGGGCTGCCGGGCTCC
1560	GAGCCCGGCAGCCCGCCTC	GAGGCGGGCTGCCGGGCTC
1561	AGCCCGGCAGCCCGCCTCG	CGAGGCGGGCTGCCGGGCT
1562	GCCCGGCAGCCCGCCTCGA	TCGAGGCGGGCTGCCGGGC
1563	CCCGGCAGCCCGCCTCGAG	CTCGAGGCGGGCTGCCGGG
1564	CCGGCAGCCCGCCTCGAGA	TCTCGAGGCGGGCTGCCGG
1565	CGGCAGCCCGCCTCGAGAT	ATCTCGAGGCGGGCTGCCG
1566	GGCAGCCCGCCTCGAGATG	CATCTCGAGGCGGGCTGCC
1567	GCAGCCCGCCTCGAGATGG	CCATCTCGAGGCGGGCTGC
1568	CAGCCCGCCTCGAGATGGA	TCCATCTCGAGGCGGGCTG
1569	AGCCCGCCTCGAGATGGAC	GTCCATCTCGAGGCGGGCT
1570	GCCCGCCTCGAGATGGACT	AGTCCATCTCGAGGCGGGC
1571	CCCGCCTCGAGATGGACTG	CAGTCCATCTCGAGGCGGG
1572	CCGCCTCGAGATGGACTGC	GCAGTCCATCTCGAGGCGG
1573	CGCCTCGAGATGGACTGCA	TGCAGTCCATCTCGAGGCG
1574	GCCTCGAGATGGACTGCAC	GTGCAGTCCATCTCGAGGC
1575	CCTCGAGATGGACTGCACC	GGTGCAGTCCATCTCGAGG
1576	CTCGAGATGGACTGCACCA	TGGTGCAGTCCATCTCGAG
1577	TCGAGATGGACTGCACCAT	ATGGTGCAGTCCATCTCGA
1578	CGAGATGGACTGCACCATG	CATGGTGCAGTCCATCTCG
1579	GAGATGGACTGCACCATGG	CCATGGTGCAGTCCATCTC
1580	AGATGGACTGCACCATGGG	CCCATGGTGCAGTCCATCT
1581	GATGGACTGCACCATGGGC	GCCCATGGTGCAGTCCATC
1582	ATGGACTGCACCATGGGCC	GGCCCATGGTGCAGTCCAT
1583	TGGACTGCACCATGGGCCG	CGGCCCATGGTGCAGTCCA
1584	GGACTGCACCATGGGCCGC	GCGGCCCATGGTGCAGTCC
1585	GACTGCACCATGGGCCGCT	AGCGGCCCATGGTGCAGTC
1586	ACTGCACCATGGGCCGCTG	CAGCGGCCCATGGTGCAGT
1587	CTGCACCATGGGCCGCTGT	ACAGCGGCCCATGGTGCAG
1588	TGCACCATGGGCCGCTGTG	CACAGCGGCCCATGGTGCA
1589	GCACCATGGGCCGCTGTGC	GCACAGCGGCCCATGGTGC
1590	CACCATGGGCCGCTGTGCC	GGCACAGCGGCCCATGGTG
1591	ACCATGGGCCGCTGTGCCT	AGGCACAGCGGCCCATGGT
1592	CCATGGGCCGCTGTGCCTG	CAGGCACAGCGGCCCATGG
1593	CATGGGCCGCTGTGCCTGG	CCAGGCACAGCGGCCCATG
1594	ATGGGCCGCTGTGCCTGGG	CCCAGGCACAGCGGCCCAT
1595	TGGGCCGCTGTGCCTGGGA	TCCCAGGCACAGCGGCCCA
1596	GGGCCGCTGTGCCTGGGAG	CTCCCAGGCACAGCGGCCC
1597	GGCCGCTGTGCCTGGGAGA	TCTCCCAGGCACAGCGGCC
1598	GCCGCTGTGCCTGGGAGAG	CTCTCCCAGGCACAGCGGC
1599	CCGCTGTGCCTGGGAGAGC	GCTCTCCCAGGCACAGCGG
1600	CGCTGTGCCTGGGAGAGCC	GGCTCTCCCAGGCACAGCG
1601	GCTGTGCCTGGGAGAGCCT	AGGCTCTCCCAGGCACAGC
1602	CTGTGCCTGGGAGAGCCTG	CAGGCTCTCCCAGGCACAG
1603	TGTGCCTGGGAGAGCCTGC	GCAGGCTCTCCCAGGCACA
1604	GTGCCTGGGAGAGCCTGCT	AGCAGGCTCTCCCAGGCAC
1605	TGCCTGGGAGAGCCTGCTC	GAGCAGGCTCTCCCAGGCA
1606	GCCTGGGAGAGCCTGCTCC	GGAGCAGGCTCTCCCAGGC
1607	CCTGGGAGAGCCTGCTCCC	GGGAGCAGGCTCTCCCAGG
1608	CTGGGAGAGCCTGCTCCCT	AGGGAGCAGGCTCTCCCAG
1609	TGGGAGAGCCTGCTCCCTT	AAGGGAGCAGGCTCTCCCA
1610	GGGAGAGCCTGCTCCCTTT	AAAGGGAGCAGGCTCTCCC
1611	GGAGAGCCTGCTCCCTTTT	AAAAGGGAGCAGGCTCTCC
1612	GAGAGCCTGCTCCCTTTTG	CAAAAGGGAGCAGGCTCTC
1613	AGAGCCTGCTCCCTTTTGG	CCAAAAGGGAGCAGGCTCT
1614	GAGCCTGCTCCCTTTTGGA	TCCAAAAGGGAGCAGGCTC
1615	AGCCTGCTCCCTTTTGGAG	CTCCAAAAGGGAGCAGGCT
1616	GCCTGCTCCCTTTTGGAGG	CCTCCAAAAGGGAGCAGGC
1617	CCTGCTCCCTTTTGGAGGG	CCCTCCAAAAGGGAGCAGG
1618	CTGCTCCCTTTTGGAGGGG	CCCCTCCAAAAGGGAGCAG
1619	TGCTCCCTTTTGGAGGGGC	GCCCCTCCAAAAGGGAGCA
1620	GCTCCCTTTTGGAGGGGCG	CGCCCCTCCAAAAGGGAGC
1621	CTCCCTTTTGGAGGGGCGT	ACGCCCCTCCAAAAGGGAG
1622	TCCCTTTTGGAGGGGCGTC	GACGCCCCTCCAAAAGGGA
1623	CCCTTTTGGAGGGGCGTCC	GGACGCCCCTCCAAAAGGG
1624	CCTTTTGGAGGGGCGTCCT	AGGACGCCCCTCCAAAAGG
1625	CTTTTGGAGGGGCGTCCTG	CAGGACGCCCCTCCAAAAG
1626	TTTTGGAGGGGCGTCCTGA	TCAGGACGCCCCTCCAAAA
1627	TTTGGAGGGGCGTCCTGAG	CTCAGGACGCCCCTCCAAA
1628	TTGGAGGGGCGTCCTGAGC	GCTCAGGACGCCCCTCCAA
1629	TGGAGGGGCGTCCTGAGCA	TGCTCAGGACGCCCCTCCA
1630	GGAGGGGCGTCCTGAGCAC	GTGCTCAGGACGCCCCTCC
1631	GAGGGGCGTCCTGAGCACC	GGTGCTCAGGACGCCCCTC
1632	AGGGGCGTCCTGAGCACCC	GGGTGCTCAGGACGCCCCT
1633	GGGGCGTCCTGAGCACCCC	GGGGTGCTCAGGACGCCCC
1634	GGGCGTCCTGAGCACCCCA	TGGGGTGCTCAGGACGCCC
1635	GGCGTCCTGAGCACCCCAG	CTGGGGTGCTCAGGACGCC
1636	GCGTCCTGAGCACCCCAGA	TCTGGGGTGCTCAGGACGC
1637	CGTCCTGAGCACCCCAGAC	GTCTGGGGTGCTCAGGACG
1638	GTCCTGAGCACCCCAGACT	AGTCTGGGGTGCTCAGGAC
1639	TCCTGAGCACCCCAGACTC	GAGTCTGGGGTGCTCAGGA
1640	CCTGAGCACCCCAGACTCC	GGAGTCTGGGGTGCTCAGG
1641	CTGAGCACCCCAGACTCCT	AGGAGTCTGGGGTGCTCAG
1642	TGAGCACCCCAGACTCCTG	CAGGAGTCTGGGGTGCTCA
1643	GAGCACCCCAGACTCCTGG	CCAGGAGTCTGGGGTGCTC
1644	AGCACCCCAGACTCCTGGC	GCCAGGAGTCTGGGGTGCT
1645	GCACCCCAGACTCCTGGCT	AGCCAGGAGTCTGGGGTGC
1646	CACCCCAGACTCCTGGCTT	AAGCCAGGAGTCTGGGGTG
1647	ACCCCAGACTCCTGGCTTC	GAAGCCAGGAGTCTGGGGT
1648	CCCCAGACTCCTGGCTTCC	GGAAGCCAGGAGTCTGGGG
1649	CCCAGACTCCTGGCTTCCC	GGGAAGCCAGGAGTCTGGG
1650	CCAGACTCCTGGCTTCCCC	GGGGAAGCCAGGAGTCTGG
1651	CAGACTCCTGGCTTCCCCC	GGGGGAAGCCAGGAGTCTG
1652	AGACTCCTGGCTTCCCCCT	AGGGGGAAGCCAGGAGTCT
1653	GACTCCTGGCTTCCCCCTG	CAGGGGGAAGCCAGGAGTC
1654	ACTCCTGGCTTCCCCCTGG	CCAGGGGGAAGCCAGGAGT
1655	CTCCTGGCTTCCCCCTGGC	GCCAGGGGGAAGCCAGGAG
1656	TCCTGGCTTCCCCCTGGCT	AGCCAGGGGGAAGCCAGGA
1657	CCTGGCTTCCCCCTGGCTT	AAGCCAGGGGGAAGCCAGG
1658	CTGGCTTCCCCCTGGCTTC	GAAGCCAGGGGGAAGCCAG
1659	TGGCTTCCCCCTGGCTTCC	GGAAGCCAGGGGGAAGCCA
1660	GGCTTCCCCCTGGCTTCCC	GGGAAGCCAGGGGGAAGCC
1661	GCTTCCCCCTGGCTTCCCC	GGGGAAGCCAGGGGGAAGC
1662	CTTCCCCCTGGCTTCCCCC	GGGGGAAGCCAGGGGGAAG
1663	TTCCCCCTGGCTTCCCCCA	TGGGGGAAGCCAGGGGGAA
1664	TCCCCCTGGCTTCCCCCAG	CTGGGGGAAGCCAGGGGGA
1665	CCCCCTGGCTTCCCCCAGG	CCTGGGGGAAGCCAGGGGG
1666	CCCCTGGCTTCCCCCAGGG	CCCTGGGGGAAGCCAGGGG
1667	CCCTGGCTTCCCCCAGGGC	GCCCTGGGGGAAGCCAGGG
1668	CCTGGCTTCCCCCAGGGCC	GGCCCTGGGGGAAGCCAGG
1669	CTGGCTTCCCCCAGGGCCC	GGGCCCTGGGGGAAGCCAG
1670	TGGCTTCCCCCAGGGCCCC	GGGGCCCTGGGGGAAGCCA
1671	GGCTTCCCCCAGGGCCCCA	TGGGGCCCTGGGGGAAGCC
1672	GCTTCCCCCAGGGCCCCAA	TTGGGGCCCTGGGGGAAGC
1673	CTTCCCCCAGGGCCCCAAG	CTTGGGGCCCTGGGGGAAG
1674	TTCCCCCAGGGCCCCAAGG	CCTTGGGGCCCTGGGGGAA
1675	TCCCCCAGGGCCCCAAGGA	TCCTTGGGGCCCTGGGGGA
1676	CCCCCAGGGCCCCAAGGAC	GTCCTTGGGGCCCTGGGGG
1677	CCCCAGGGCCCCAAGGACA	TGTCCTTGGGGCCCTGGGG
1678	CCCAGGGCCCCAAGGACAT	ATGTCCTTGGGGCCCTGGG
1679	CCAGGGCCCCAAGGACATG	CATGTCCTTGGGGCCCTGG
1680	CAGGGCCCCAAGGACATGC	GCATGTCCTTGGGGCCCTG
1681	AGGGCCCCAAGGACATGCT	AGCATGTCCTTGGGGCCCT
1682	GGGCCCCAAGGACATGCTC	GAGCATGTCCTTGGGGCCC
1683	GGCCCCAAGGACATGCTCC	GGAGCATGTCCTTGGGGCC
1684	GCCCCAAGGACATGCTCCC	GGGAGCATGTCCTTGGGGC
1685	CCCCAAGGACATGCTCCCA	TGGGAGCATGTCCTTGGGG
1686	CCCAAGGACATGCTCCCAC	GTGGGAGCATGTCCTTGGG
1687	CCAAGGACATGCTCCCACT	AGTGGGAGCATGTCCTTGG
1688	CAAGGACATGCTCCCACTT	AAGTGGGAGCATGTCCTTG
1689	AAGGACATGCTCCCACTTG	CAAGTGGGAGCATGTCCTT
1690	AGGACATGCTCCCACTTGT	ACAAGTGGGAGCATGTCCT
1691	GGACATGCTCCCACTTGTG	CACAAGTGGGAGCATGTCC
1692	GACATGCTCCCACTTGTGG	CCACAAGTGGGAGCATGTC
1693	ACATGCTCCCACTTGTGGA	TCCACAAGTGGGAGCATGT
1694	CATGCTCCCACTTGTGGAG	CTCCACAAGTGGGAGCATG
1695	ATGCTCCCACTTGTGGAGG	CCTCCACAAGTGGGAGCAT
1696	TGCTCCCACTTGTGGAGGG	CCCTCCACAAGTGGGAGCA
1697	GCTCCCACTTGTGGAGGGC	GCCCTCCACAAGTGGGAGC
1698	CTCCCACTTGTGGAGGGCG	CGCCCTCCACAAGTGGGAG
1699	TCCCACTTGTGGAGGGCGA	TCGCCCTCCACAAGTGGGA
1700	CCCACTTGTGGAGGGCGAG	CTCGCCCTCCACAAGTGGG
1701	CCACTTGTGGAGGGCGAGG	CCTCGCCCTCCACAAGTGG
1702	CACTTGTGGAGGGCGAGGG	CCCTCGCCCTCCACAAGTG
1703	ACTTGTGGAGGGCGAGGGC	GCCCTCGCCCTCCACAAGT
1704	CTTGTGGAGGGCGAGGGCC	GGCCCTCGCCCTCCACAAG
1705	TTGTGGAGGGCGAGGGCCC	GGGCCCTCGCCCTCCACAA
1706	TGTGGAGGGCGAGGGCCCC	GGGGCCCTCGCCCTCCACA
1707	GTGGAGGGCGAGGGCCCCC	GGGGGCCCTCGCCCTCCAC
1708	TGGAGGGCGAGGGCCCCCA	TGGGGGCCCTCGCCCTCCA
1709	GGAGGGCGAGGGCCCCCAG	CTGGGGGCCCTCGCCCTCC
1710	GAGGGCGAGGGCCCCCAGA	TCTGGGGGCCCTCGCCCTC
1711	AGGGCGAGGGCCCCCAGAA	TTCTGGGGGCCCTCGCCCT
1712	GGGCGAGGGCCCCCAGAAT	ATTCTGGGGGCCCTCGCCC
1713	GGCGAGGGCCCCCAGAATG	CATTCTGGGGGCCCTCGCC
1714	GCGAGGGCCCCCAGAATGG	CCATTCTGGGGGCCCTCGC
1715	CGAGGGCCCCCAGAATGGG	CCCATTCTGGGGGCCCTCG
1716	GAGGGCCCCCAGAATGGGG	CCCCATTCTGGGGGCCCTC
1717	AGGGCCCCCAGAATGGGGA	TCCCCATTCTGGGGGCCCT
1718	GGGCCCCCAGAATGGGGAG	CTCCCCATTCTGGGGGCCC
1719	GGCCCCCAGAATGGGGAGA	TCTCCCCATTCTGGGGGCC
1720	GCCCCCAGAATGGGGAGAG	CTCTCCCCATTCTGGGGGC
1721	CCCCCAGAATGGGGAGAGG	CCTCTCCCCATTCTGGGGG
1722	CCCCAGAATGGGGAGAGGA	TCCTCTCCCCATTCTGGGG
1723	CCCAGAATGGGGAGAGGAA	TTCCTCTCCCCATTCTGGG
1724	CCAGAATGGGGAGAGGAAG	CTTCCTCTCCCCATTCTGG
1725	CAGAATGGGGAGAGGAAGG	CCTTCCTCTCCCCATTCTG
1726	AGAATGGGGAGAGGAAGGT	ACCTTCCTCTCCCCATTCT
1727	GAATGGGGAGAGGAAGGTC	GACCTTCCTCTCCCCATTC
1728	AATGGGGAGAGGAAGGTCA	TGACCTTCCTCTCCCCATT
1729	ATGGGGAGAGGAAGGTCAA	TTGACCTTCCTCTCCCCAT
1730	TGGGGAGAGGAAGGTCAAC	GTTGACCTTCCTCTCCCCA
1731	GGGGAGAGGAAGGTCAACT	AGTTGACCTTCCTCTCCCC
1732	GGGAGAGGAAGGTCAACTG	CAGTTGACCTTCCTCTCCC
1733	GGAGAGGAAGGTCAACTGG	CCAGTTGACCTTCCTCTCC
1734	GAGAGGAAGGTCAACTGGC	GCCAGTTGACCTTCCTCTC
1735	AGAGGAAGGTCAACTGGCT	AGCCAGTTGACCTTCCTCT
1736	GAGGAAGGTCAACTGGCTG	CAGCCAGTTGACCTTCCTC
1737	AGGAAGGTCAACTGGCTGG	CCAGCCAGTTGACCTTCCT
1738	GGAAGGTCAACTGGCTGGG	CCCAGCCAGTTGACCTTCC
1739	GAAGGTCAACTGGCTGGGC	GCCCAGCCAGTTGACCTTC
1740	AAGGTCAACTGGCTGGGCA	TGCCCAGCCAGTTGACCTT
1741	AGGTCAACTGGCTGGGCAG	CTGCCCAGCCAGTTGACCT
1742	GGTCAACTGGCTGGGCAGC	GCTGCCCAGCCAGTTGACC
1743	GTCAACTGGCTGGGCAGCA	TGCTGCCCAGCCAGTTGAC
1744	TCAACTGGCTGGGCAGCAA	TTGCTGCCCAGCCAGTTGA
1745	CAACTGGCTGGGCAGCAAA	TTTGCTGCCCAGCCAGTTG
1746	AACTGGCTGGGCAGCAAAG	CTTTGCTGCCCAGCCAGTT
1747	ACTGGCTGGGCAGCAAAGA	TCTTTGCTGCCCAGCCAGT
1748	CTGGCTGGGCAGCAAAGAG	CTCTTTGCTGCCCAGCCAG
1749	TGGCTGGGCAGCAAAGAGG	CCTCTTTGCTGCCCAGCCA
1750	GGCTGGGCAGCAAAGAGGG	CCCTCTTTGCTGCCCAGCC
1751	GCTGGGCAGCAAAGAGGGA	TCCCTCTTTGCTGCCCAGC
1752	CTGGGCAGCAAAGAGGGAC	GTCCCTCTTTGCTGCCCAG
1753	TGGGCAGCAAAGAGGGACT	AGTCCCTCTTTGCTGCCCA
1754	GGGCAGCAAAGAGGGACTG	CAGTCCCTCTTTGCTGCCC
1755	GGCAGCAAAGAGGGACTGC	GCAGTCCCTCTTTGCTGCC
1756	GCAGCAAAGAGGGACTGCG	CGCAGTCCCTCTTTGCTGC
1757	CAGCAAAGAGGGACTGCGC	GCGCAGTCCCTCTTTGCTG
1758	AGCAAAGAGGGACTGCGCT	AGCGCAGTCCCTCTTTGCT
1759	GCAAAGAGGGACTGCGCTG	CAGCGCAGTCCCTCTTTGC
1760	CAAAGAGGGACTGCGCTGG	CCAGCGCAGTCCCTCTTTG
1761	AAAGAGGGACTGCGCTGGA	TCCAGCGCAGTCCCTCTTT
1762	AAGAGGGACTGCGCTGGAA	TTCCAGCGCAGTCCCTCTT
1763	AGAGGGACTGCGCTGGAAG	CTTCCAGCGCAGTCCCTCT
1764	GAGGGACTGCGCTGGAAGG	CCTTCCAGCGCAGTCCCTC
1765	AGGGACTGCGCTGGAAGGA	TCCTTCCAGCGCAGTCCCT
1766	GGGACTGCGCTGGAAGGAG	CTCCTTCCAGCGCAGTCCC
1767	GGACTGCGCTGGAAGGAGG	CCTCCTTCCAGCGCAGTCC
1768	GACTGCGCTGGAAGGAGGC	GCCTCCTTCCAGCGCAGTC
1769	ACTGCGCTGGAAGGAGGCC	GGCCTCCTTCCAGCGCAGT
1770	CTGCGCTGGAAGGAGGCCA	TGGCCTCCTTCCAGCGCAG
1771	TGCGCTGGAAGGAGGCCAT	ATGGCCTCCTTCCAGCGCA
1772	GCGCTGGAAGGAGGCCATG	CATGGCCTCCTTCCAGCGC
1773	CGCTGGAAGGAGGCCATGC	GCATGGCCTCCTTCCAGCG
1774	GCTGGAAGGAGGCCATGCT	AGCATGGCCTCCTTCCAGC
1775	CTGGAAGGAGGCCATGCTT	AAGCATGGCCTCCTTCCAG
1776	TGGAAGGAGGCCATGCTTA	TAAGCATGGCCTCCTTCCA
1777	GGAAGGAGGCCATGCTTAC	GTAAGCATGGCCTCCTTCC
1778	GAAGGAGGCCATGCTTACC	GGTAAGCATGGCCTCCTTC
1779	AAGGAGGCCATGCTTACCC	GGGTAAGCATGGCCTCCTT
1780	AGGAGGCCATGCTTACCCA	TGGGTAAGCATGGCCTCCT
1781	GGAGGCCATGCTTACCCAT	ATGGGTAAGCATGGCCTCC
1782	GAGGCCATGCTTACCCATC	GATGGGTAAGCATGGCCTC
1783	AGGCCATGCTTACCCATCC	GGATGGGTAAGCATGGCCT
1784	GGCCATGCTTACCCATCCG	CGGATGGGTAAGCATGGCC
1785	GCCATGCTTACCCATCCGC	GCGGATGGGTAAGCATGGC
1786	CCATGCTTACCCATCCGCT	AGCGGATGGGTAAGCATGG
1787	CATGCTTACCCATCCGCTG	CAGCGGATGGGTAAGCATG
1788	ATGCTTACCCATCCGCTGG	CCAGCGGATGGGTAAGCAT
1789	TGCTTACCCATCCGCTGGC	GCCAGCGGATGGGTAAGCA
1790	GCTTACCCATCCGCTGGCA	TGCCAGCGGATGGGTAAGC
1791	CTTACCCATCCGCTGGCAT	ATGCCAGCGGATGGGTAAG
1792	TTACCCATCCGCTGGCATT	AATGCCAGCGGATGGGTAA
1793	TACCCATCCGCTGGCATTC	GAATGCCAGCGGATGGGTA
1794	ACCCATCCGCTGGCATTCT	AGAATGCCAGCGGATGGGT
1795	CCCATCCGCTGGCATTCTG	CAGAATGCCAGCGGATGGG
1796	CCATCCGCTGGCATTCTGC	GCAGAATGCCAGCGGATGG
1797	CATCCGCTGGCATTCTGCG	CGCAGAATGCCAGCGGATG
1798	ATCCGCTGGCATTCTGCGG	CCGCAGAATGCCAGCGGAT
1799	TCCGCTGGCATTCTGCGGG	CCCGCAGAATGCCAGCGGA
1800	CCGCTGGCATTCTGCGGGC	GCCCGCAGAATGCCAGCGG
1801	CGCTGGCATTCTGCGGGCC	GGCCCGCAGAATGCCAGCG
1802	GCTGGCATTCTGCGGGCCA	TGGCCCGCAGAATGCCAGC
1803	CTGGCATTCTGCGGGCCAG	CTGGCCCGCAGAATGCCAG
1804	TGGCATTCTGCGGGCCAGC	GCTGGCCCGCAGAATGCCA
1805	GGCATTCTGCGGGCCAGCG	CGCTGGCCCGCAGAATGCC
1806	GCATTCTGCGGGCCAGCGT	ACGCTGGCCCGCAGAATGC
1807	CATTCTGCGGGCCAGCGTG	CACGCTGGCCCGCAGAATG
1808	ATTCTGCGGGCCAGCGTGC	GCACGCTGGCCCGCAGAAT
1809	TTCTGCGGGCCAGCGTGCC	GGCACGCTGGCCCGCAGAA
1810	TCTGCGGGCCAGCGTGCCC	GGGCACGCTGGCCCGCAGA
1811	CTGCGGGCCAGCGTGCCCA	TGGGCACGCTGGCCCGCAG
1812	TGCGGGCCAGCGTGCCCAC	GTGGGCACGCTGGCCCGCA
1813	GCGGGCCAGCGTGCCCACC	GGTGGGCACGCTGGCCCGC
1814	CGGGCCAGCGTGCCCACCT	AGGTGGGCACGCTGGCCCG
1815	GGGCCAGCGTGCCCACCTC	GAGGTGGGCACGCTGGCCC
1816	GGCCAGCGTGCCCACCTCG	CGAGGTGGGCACGCTGGCC
1817	GCCAGCGTGCCCACCTCGC	GCGAGGTGGGCACGCTGGC
1818	CCAGCGTGCCCACCTCGCT	AGCGAGGTGGGCACGCTGG
1819	CAGCGTGCCCACCTCGCTG	CAGCGAGGTGGGCACGCTG
1820	AGCGTGCCCACCTCGCTGT	ACAGCGAGGTGGGCACGCT
1821	GCGTGCCCACCTCGCTGTG	CACAGCGAGGTGGGCACGC
1822	CGTGCCCACCTCGCTGTGG	CCACAGCGAGGTGGGCACG
1823	GTGCCCACCTCGCTGTGGC	GCCACAGCGAGGTGGGCAC
1824	TGCCCACCTCGCTGTGGCC	GGCCACAGCGAGGTGGGCA
1825	GCCCACCTCGCTGTGGCCC	GGGCCACAGCGAGGTGGGC
1826	CCCACCTCGCTGTGGCCCC	GGGGCCACAGCGAGGTGGG
1827	CCACCTCGCTGTGGCCCCC	GGGGGCCACAGCGAGGTGG
1828	CACCTCGCTGTGGCCCCCT	AGGGGGCCACAGCGAGGTG
1829	ACCTCGCTGTGGCCCCCTG	CAGGGGGCCACAGCGAGGT
1830	CCTCGCTGTGGCCCCCTGA	TCAGGGGGCCACAGCGAGG
1831	CTCGCTGTGGCCCCCTGAT	ATCAGGGGGCCACAGCGAG
1832	TCGCTGTGGCCCCCTGATG	CATCAGGGGGCCACAGCGA
1833	CGCTGTGGCCCCCTGATGC	GCATCAGGGGGCCACAGCG
1834	GCTGTGGCCCCCTGATGCC	GGCATCAGGGGGCCACAGC
1835	CTGTGGCCCCCTGATGCCT	AGGCATCAGGGGGCCACAG
1836	TGTGGCCCCCTGATGCCTG	CAGGCATCAGGGGGCCACA
1837	GTGGCCCCCTGATGCCTGA	TCAGGCATCAGGGGGCCAC
1838	TGGCCCCCTGATGCCTGAG	CTCAGGCATCAGGGGGCCA
1839	GGCCCCCTGATGCCTGAGC	GCTCAGGCATCAGGGGGCC
1840	GCCCCCTGATGCCTGAGCA	TGCTCAGGCATCAGGGGGC
1841	CCCCCTGATGCCTGAGCAT	ATGCTCAGGCATCAGGGGG
1842	CCCCTGATGCCTGAGCATA	TATGCTCAGGCATCAGGGG
1843	CCCTGATGCCTGAGCATAG	CTATGCTCAGGCATCAGGG
1844	CCTGATGCCTGAGCATAGT	ACTATGCTCAGGCATCAGG
1845	CTGATGCCTGAGCATAGTG	CACTATGCTCAGGCATCAG
1846	TGATGCCTGAGCATAGTGG	CCACTATGCTCAGGCATCA
1847	GATGCCTGAGCATAGTGGT	ACCACTATGCTCAGGCATC
1848	ATGCCTGAGCATAGTGGTG	CACCACTATGCTCAGGCAT
1849	TGCCTGAGCATAGTGGTGG	CCACCACTATGCTCAGGCA
1850	GCCTGAGCATAGTGGTGGC	GCCACCACTATGCTCAGGC
1851	CCTGAGCATAGTGGTGGCC	GGCCACCACTATGCTCAGG
1852	CTGAGCATAGTGGTGGCCA	TGGCCACCACTATGCTCAG
1853	TGAGCATAGTGGTGGCCAT	ATGGCCACCACTATGCTCA
1854	GAGCATAGTGGTGGCCATC	GATGGCCACCACTATGCTC
1855	AGCATAGTGGTGGCCATCT	AGATGGCCACCACTATGCT
1856	GCATAGTGGTGGCCATCTC	GAGATGGCCACCACTATGC
1857	CATAGTGGTGGCCATCTCA	TGAGATGGCCACCACTATG
1858	ATAGTGGTGGCCATCTCAA	TTGAGATGGCCACCACTAT
1859	TAGTGGTGGCCATCTCAAG	CTTGAGATGGCCACCACTA
1860	AGTGGTGGCCATCTCAAGA	TCTTGAGATGGCCACCACT
1861	GTGGTGGCCATCTCAAGAG	CTCTTGAGATGGCCACCAC
1862	TGGTGGCCATCTCAAGAGT	ACTCTTGAGATGGCCACCA
1863	GGTGGCCATCTCAAGAGTG	CACTCTTGAGATGGCCACC
1864	GTGGCCATCTCAAGAGTGA	TCACTCTTGAGATGGCCAC
1865	TGGCCATCTCAAGAGTGAC	GTCACTCTTGAGATGGCCA
1866	GGCCATCTCAAGAGTGACC	GGTCACTCTTGAGATGGCC
1867	GCCATCTCAAGAGTGACCC	GGGTCACTCTTGAGATGGC
1868	CCATCTCAAGAGTGACCCT	AGGGTCACTCTTGAGATGG
1869	CATCTCAAGAGTGACCCTG	CAGGGTCACTCTTGAGATG
1870	ATCTCAAGAGTGACCCTGT	ACAGGGTCACTCTTGAGAT
1871	TCTCAAGAGTGACCCTGTG	CACAGGGTCACTCTTGAGA
1872	CTCAAGAGTGACCCTGTGG	CCACAGGGTCACTCTTGAG
1873	TCAAGAGTGACCCTGTGGC	GCCACAGGGTCACTCTTGA
1874	CAAGAGTGACCCTGTGGCC	GGCCACAGGGTCACTCTTG
1875	AAGAGTGACCCTGTGGCCT	AGGCCACAGGGTCACTCTT
1876	AGAGTGACCCTGTGGCCTT	AAGGCCACAGGGTCACTCT
1877	GAGTGACCCTGTGGCCTTC	GAAGGCCACAGGGTCACTC
1878	AGTGACCCTGTGGCCTTCC	GGAAGGCCACAGGGTCACT
1879	GTGACCCTGTGGCCTTCCG	CGGAAGGCCACAGGGTCAC
1880	TGACCCTGTGGCCTTCCGG	CCGGAAGGCCACAGGGTCA
1881	GACCCTGTGGCCTTCCGGC	GCCGGAAGGCCACAGGGTC
1882	ACCCTGTGGCCTTCCGGCC	GGCCGGAAGGCCACAGGGT
1883	CCCTGTGGCCTTCCGGCCC	GGGCCGGAAGGCCACAGGG
1884	CCTGTGGCCTTCCGGCCCT	AGGGCCGGAAGGCCACAGG
1885	CTGTGGCCTTCCGGCCCTG	CAGGGCCGGAAGGCCACAG
1886	TGTGGCCTTCCGGCCCTGG	CCAGGGCCGGAAGGCCACA
1887	GTGGCCTTCCGGCCCTGGC	GCCAGGGCCGGAAGGCCAC
1888	TGGCCTTCCGGCCCTGGCA	TGCCAGGGCCGGAAGGCCA
1889	GGCCTTCCGGCCCTGGCAC	GTGCCAGGGCCGGAAGGCC
1890	GCCTTCCGGCCCTGGCACT	AGTGCCAGGGCCGGAAGGC
1891	CCTTCCGGCCCTGGCACTG	CAGTGCCAGGGCCGGAAGG
1892	CTTCCGGCCCTGGCACTGC	GCAGTGCCAGGGCCGGAAG
1893	TTCCGGCCCTGGCACTGCC	GGCAGTGCCAGGGCCGGAA
1894	TCCGGCCCTGGCACTGCCC	GGGCAGTGCCAGGGCCGGA
1895	CCGGCCCTGGCACTGCCCT	AGGGCAGTGCCAGGGCCGG
1896	CGGCCCTGGCACTGCCCTT	AAGGGCAGTGCCAGGGCCG
1897	GGCCCTGGCACTGCCCTTT	AAAGGGCAGTGCCAGGGCC
1898	GCCCTGGCACTGCCCTTTC	GAAAGGGCAGTGCCAGGGC
1899	CCCTGGCACTGCCCTTTCC	GGAAAGGGCAGTGCCAGGG
1900	CCTGGCACTGCCCTTTCCT	AGGAAAGGGCAGTGCCAGG
1901	CTGGCACTGCCCTTTCCTT	AAGGAAAGGGCAGTGCCAG
1902	TGGCACTGCCCTTTCCTTC	GAAGGAAAGGGCAGTGCCA
1903	GGCACTGCCCTTTCCTTCT	AGAAGGAAAGGGCAGTGCC
1904	GCACTGCCCTTTCCTTCTG	CAGAAGGAAAGGGCAGTGC
1905	CACTGCCCTTTCCTTCTGG	CCAGAAGGAAAGGGCAGTG
1906	ACTGCCCTTTCCTTCTGGA	TCCAGAAGGAAAGGGCAGT
1907	CTGCCCTTTCCTTCTGGAG	CTCCAGAAGGAAAGGGCAG
1908	TGCCCTTTCCTTCTGGAGA	TCTCCAGAAGGAAAGGGCA
1909	GCCCTTTCCTTCTGGAGAC	GTCTCCAGAAGGAAAGGGC
1910	CCCTTTCCTTCTGGAGACC	GGTCTCCAGAAGGAAAGGG
1911	CCTTTCCTTCTGGAGACCA	TGGTCTCCAGAAGGAAAGG
1912	CTTTCCTTCTGGAGACCAA	TTGGTCTCCAGAAGGAAAG
1913	TTTCCTTCTGGAGACCAAG	CTTGGTCTCCAGAAGGAAA
1914	TTCCTTCTGGAGACCAAGA	TCTTGGTCTCCAGAAGGAA
1915	TCCTTCTGGAGACCAAGAT	ATCTTGGTCTCCAGAAGGA
1916	CCTTCTGGAGACCAAGATC	GATCTTGGTCTCCAGAAGG
1917	CTTCTGGAGACCAAGATCC	GGATCTTGGTCTCCAGAAG
1918	TTCTGGAGACCAAGATCCT	AGGATCTTGGTCTCCAGAA
1919	TCTGGAGACCAAGATCCTG	CAGGATCTTGGTCTCCAGA
1920	CTGGAGACCAAGATCCTGG	CCAGGATCTTGGTCTCCAG
1921	TGGAGACCAAGATCCTGGA	TCCAGGATCTTGGTCTCCA
1922	GGAGACCAAGATCCTGGAG	CTCCAGGATCTTGGTCTCC
1923	GAGACCAAGATCCTGGAGC	GCTCCAGGATCTTGGTCTC
1924	AGACCAAGATCCTGGAGCG	CGCTCCAGGATCTTGGTCT
1925	GACCAAGATCCTGGAGCGA	TCGCTCCAGGATCTTGGTC
1926	ACCAAGATCCTGGAGCGAG	CTCGCTCCAGGATCTTGGT
1927	CCAAGATCCTGGAGCGAGC	GCTCGCTCCAGGATCTTGG
1928	CAAGATCCTGGAGCGAGCT	AGCTCGCTCCAGGATCTTG
1929	AAGATCCTGGAGCGAGCTC	GAGCTCGCTCCAGGATCTT
1930	AGATCCTGGAGCGAGCTCC	GGAGCTCGCTCCAGGATCT
1931	GATCCTGGAGCGAGCTCCC	GGGAGCTCGCTCCAGGATC
1932	ATCCTGGAGCGAGCTCCCT	AGGGAGCTCGCTCCAGGAT
1933	TCCTGGAGCGAGCTCCCTT	AAGGGAGCTCGCTCCAGGA
1934	CCTGGAGCGAGCTCCCTTC	GAAGGGAGCTCGCTCCAGG
1935	CTGGAGCGAGCTCCCTTCT	AGAAGGGAGCTCGCTCCAG
1936	TGGAGCGAGCTCCCTTCTG	CAGAAGGGAGCTCGCTCCA
1937	GGAGCGAGCTCCCTTCTGG	CCAGAAGGGAGCTCGCTCC
1938	GAGCGAGCTCCCTTCTGGG	CCCAGAAGGGAGCTCGCTC
1939	AGCGAGCTCCCTTCTGGGT	ACCCAGAAGGGAGCTCGCT
1940	GCGAGCTCCCTTCTGGGTG	CACCCAGAAGGGAGCTCGC
1941	CGAGCTCCCTTCTGGGTGC	GCACCCAGAAGGGAGCTCG
1942	GAGCTCCCTTCTGGGTGCC	GGCACCCAGAAGGGAGCTC
1943	AGCTCCCTTCTGGGTGCCC	GGGCACCCAGAAGGGAGCT
1944	GCTCCCTTCTGGGTGCCCA	TGGGCACCCAGAAGGGAGC
1945	CTCCCTTCTGGGTGCCCAC	GTGGGCACCCAGAAGGGAG
1946	TCCCTTCTGGGTGCCCACC	GGTGGGCACCCAGAAGGGA
1947	CCCTTCTGGGTGCCCACCT	AGGTGGGCACCCAGAAGGG
1948	CCTTCTGGGTGCCCACCTG	CAGGTGGGCACCCAGAAGG
1949	CTTCTGGGTGCCCACCTGC	GCAGGTGGGCACCCAGAAG
1950	TTCTGGGTGCCCACCTGCT	AGCAGGTGGGCACCCAGAA
1951	TCTGGGTGCCCACCTGCTT	AAGCAGGTGGGCACCCAGA
1952	CTGGGTGCCCACCTGCTTG	CAAGCAGGTGGGCACCCAG
1953	TGGGTGCCCACCTGCTTGC	GCAAGCAGGTGGGCACCCA
1954	GGGTGCCCACCTGCTTGCC	GGCAAGCAGGTGGGCACCC
1955	GGTGCCCACCTGCTTGCCA	TGGCAAGCAGGTGGGCACC
1956	GTGCCCACCTGCTTGCCAC	GTGGCAAGCAGGTGGGCAC
1957	TGCCCACCTGCTTGCCACC	GGTGGCAAGCAGGTGGGCA
1958	GCCCACCTGCTTGCCACCC	GGGTGGCAAGCAGGTGGGC
1959	CCCACCTGCTTGCCACCCT	AGGGTGGCAAGCAGGTGGG
1960	CCACCTGCTTGCCACCCTA	TAGGGTGGCAAGCAGGTGG
1961	CACCTGCTTGCCACCCTAC	GTAGGGTGGCAAGCAGGTG
1962	ACCTGCTTGCCACCCTACC	GGTAGGGTGGCAAGCAGGT
1963	CCTGCTTGCCACCCTACCT	AGGTAGGGTGGCAAGCAGG
1964	CTGCTTGCCACCCTACCTA	TAGGTAGGGTGGCAAGCAG
1965	TGCTTGCCACCCTACCTAG	CTAGGTAGGGTGGCAAGCA
1966	GCTTGCCACCCTACCTAGT	ACTAGGTAGGGTGGCAAGC
1967	CTTGCCACCCTACCTAGTG	CACTAGGTAGGGTGGCAAG
1968	TTGCCACCCTACCTAGTGT	ACACTAGGTAGGGTGGCAA
1969	TGCCACCCTACCTAGTGTC	GACACTAGGTAGGGTGGCA
1970	GCCACCCTACCTAGTGTCT	AGACACTAGGTAGGGTGGC
1971	CCACCCTACCTAGTGTCTG	CAGACACTAGGTAGGGTGG
1972	CACCCTACCTAGTGTCTGG	CCAGACACTAGGTAGGGTG
1973	ACCCTACCTAGTGTCTGGC	GCCAGACACTAGGTAGGGT
1974	CCCTACCTAGTGTCTGGCC	GGCCAGACACTAGGTAGGG
1975	CCTACCTAGTGTCTGGCCT	AGGCCAGACACTAGGTAGG
1976	CTACCTAGTGTCTGGCCTG	CAGGCCAGACACTAGGTAG
1977	TACCTAGTGTCTGGCCTGC	GCAGGCCAGACACTAGGTA
1978	ACCTAGTGTCTGGCCTGCC	GGCAGGCCAGACACTAGGT
1979	CCTAGTGTCTGGCCTGCCC	GGGCAGGCCAGACACTAGG
1980	CTAGTGTCTGGCCTGCCCC	GGGGCAGGCCAGACACTAG
1981	TAGTGTCTGGCCTGCCCCC	GGGGGCAGGCCAGACACTA
1982	AGTGTCTGGCCTGCCCCCA	TGGGGGCAGGCCAGACACT
1983	GTGTCTGGCCTGCCCCCAG	CTGGGGGCAGGCCAGACAC
1984	TGTCTGGCCTGCCCCCAGA	TCTGGGGGCAGGCCAGACA
1985	GTCTGGCCTGCCCCCAGAG	CTCTGGGGGCAGGCCAGAC
1986	TCTGGCCTGCCCCCAGAGC	GCTCTGGGGGCAGGCCAGA
1987	CTGGCCTGCCCCCAGAGCA	TGCTCTGGGGGCAGGCCAG
1988	TGGCCTGCCCCCAGAGCAT	ATGCTCTGGGGGCAGGCCA
1989	GGCCTGCCCCCAGAGCATC	GATGCTCTGGGGGCAGGCC
1990	GCCTGCCCCCAGAGCATCC	GGATGCTCTGGGGGCAGGC
1991	CCTGCCCCCAGAGCATCCA	TGGATGCTCTGGGGGCAGG
1992	CTGCCCCCAGAGCATCCAT	ATGGATGCTCTGGGGGCAG
1993	TGCCCCCAGAGCATCCATG	CATGGATGCTCTGGGGGCA
1994	GCCCCCAGAGCATCCATGT	ACATGGATGCTCTGGGGGC
1995	CCCCCAGAGCATCCATGTG	CACATGGATGCTCTGGGGG
1996	CCCCAGAGCATCCATGTGA	TCACATGGATGCTCTGGGG
1997	CCCAGAGCATCCATGTGAC	GTCACATGGATGCTCTGGG
1998	CCAGAGCATCCATGTGACT	AGTCACATGGATGCTCTGG
1999	CAGAGCATCCATGTGACTG	CAGTCACATGGATGCTCTG
2000	AGAGCATCCATGTGACTGG	CCAGTCACATGGATGCTCT
2001	GAGCATCCATGTGACTGGC	GCCAGTCACATGGATGCTC
2002	AGCATCCATGTGACTGGCC	GGCCAGTCACATGGATGCT
2003	GCATCCATGTGACTGGCCC	GGGCCAGTCACATGGATGC
2004	CATCCATGTGACTGGCCCC	GGGGCCAGTCACATGGATG
2005	ATCCATGTGACTGGCCCCT	AGGGGCCAGTCACATGGAT
2006	TCCATGTGACTGGCCCCTG	CAGGGGCCAGTCACATGGA
2007	CCATGTGACTGGCCCCTGA	TCAGGGGCCAGTCACATGG
2008	CATGTGACTGGCCCCTGAC	GTCAGGGGCCAGTCACATG
2009	ATGTGACTGGCCCCTGACC	GGTCAGGGGCCAGTCACAT
2010	TGTGACTGGCCCCTGACCC	GGGTCAGGGGCCAGTCACA
2011	GTGACTGGCCCCTGACCCC	GGGGTCAGGGGCCAGTCAC
2012	TGACTGGCCCCTGACCCCG	CGGGGTCAGGGGCCAGTCA
2013	GACTGGCCCCTGACCCCGC	GCGGGGTCAGGGGCCAGTC
2014	ACTGGCCCCTGACCCCGCA	TGCGGGGTCAGGGGCCAGT
2015	CTGGCCCCTGACCCCGCAC	GTGCGGGGTCAGGGGCCAG
2016	TGGCCCCTGACCCCGCACC	GGTGCGGGGTCAGGGGCCA
2017	GGCCCCTGACCCCGCACCC	GGGTGCGGGGTCAGGGGCC
2018	GCCCCTGACCCCGCACCCC	GGGGTGCGGGGTCAGGGGC
2019	CCCCTGACCCCGCACCCCT	AGGGGTGCGGGGTCAGGGG
2020	CCCTGACCCCGCACCCCTG	CAGGGGTGCGGGGTCAGGG
2021	CCTGACCCCGCACCCCTGG	CCAGGGGTGCGGGGTCAGG
2022	CTGACCCCGCACCCCTGGG	CCCAGGGGTGCGGGGTCAG
2023	TGACCCCGCACCCCTGGGT	ACCCAGGGGTGCGGGGTCA
2024	GACCCCGCACCCCTGGGTA	TACCCAGGGGTGCGGGGTC
2025	ACCCCGCACCCCTGGGTAT	ATACCCAGGGGTGCGGGGT
2026	CCCCGCACCCCTGGGTATA	TATACCCAGGGGTGCGGGG
2027	CCCGCACCCCTGGGTATAC	GTATACCCAGGGGTGCGGG
2028	CCGCACCCCTGGGTATACT	AGTATACCCAGGGGTGCGG
2029	CGCACCCCTGGGTATACTC	GAGTATACCCAGGGGTGCG
2030	GCACCCCTGGGTATACTCC	GGAGTATACCCAGGGGTGC
2031	CACCCCTGGGTATACTCCG	CGGAGTATACCCAGGGGTG
2032	ACCCCTGGGTATACTCCGG	CCGGAGTATACCCAGGGGT
2033	CCCCTGGGTATACTCCGGG	CCCGGAGTATACCCAGGGG
2034	CCCTGGGTATACTCCGGGG	CCCCGGAGTATACCCAGGG
2035	CCTGGGTATACTCCGGGGG	CCCCCGGAGTATACCCAGG
2036	CTGGGTATACTCCGGGGGC	GCCCCCGGAGTATACCCAG
2037	TGGGTATACTCCGGGGGCC	GGCCCCCGGAGTATACCCA
2038	GGGTATACTCCGGGGGCCA	TGGCCCCCGGAGTATACCC
2039	GGTATACTCCGGGGGCCAG	CTGGCCCCCGGAGTATACC
2040	GTATACTCCGGGGGCCAGC	GCTGGCCCCCGGAGTATAC
2041	TATACTCCGGGGGCCAGCC	GGCTGGCCCCCGGAGTATA
2042	ATACTCCGGGGGCCAGCCC	GGGCTGGCCCCCGGAGTAT
2043	TACTCCGGGGGCCAGCCCA	TGGGCTGGCCCCCGGAGTA
2044	ACTCCGGGGGCCAGCCCAA	TTGGGCTGGCCCCCGGAGT
2045	CTCCGGGGGCCAGCCCAAA	TTTGGGCTGGCCCCCGGAG
2046	TCCGGGGGCCAGCCCAAAG	CTTTGGGCTGGCCCCCGGA
2047	CCGGGGGCCAGCCCAAAGT	ACTTTGGGCTGGCCCCCGG
2048	CGGGGGCCAGCCCAAAGTG	CACTTTGGGCTGGCCCCCG
2049	GGGGGCCAGCCCAAAGTGC	GCACTTTGGGCTGGCCCCC
2050	GGGGCCAGCCCAAAGTGCC	GGCACTTTGGGCTGGCCCC
2051	GGGCCAGCCCAAAGTGCCC	GGGCACTTTGGGCTGGCCC
2052	GGCCAGCCCAAAGTGCCCT	AGGGCACTTTGGGCTGGCC
2053	GCCAGCCCAAAGTGCCCTC	GAGGGCACTTTGGGCTGGC
2054	CCAGCCCAAAGTGCCCTCT	AGAGGGCACTTTGGGCTGG
2055	CAGCCCAAAGTGCCCTCTG	CAGAGGGCACTTTGGGCTG
2056	AGCCCAAAGTGCCCTCTGC	GCAGAGGGCACTTTGGGCT
2057	GCCCAAAGTGCCCTCTGCC	GGCAGAGGGCACTTTGGGC
2058	CCCAAAGTGCCCTCTGCCT	AGGCAGAGGGCACTTTGGG
2059	CCAAAGTGCCCTCTGCCTT	AAGGCAGAGGGCACTTTGG
2060	CAAAGTGCCCTCTGCCTTC	GAAGGCAGAGGGCACTTTG
2061	AAAGTGCCCTCTGCCTTCA	TGAAGGCAGAGGGCACTTT
2062	AAGTGCCCTCTGCCTTCAG	CTGAAGGCAGAGGGCACTT
2063	AGTGCCCTCTGCCTTCAGC	GCTGAAGGCAGAGGGCACT
2064	GTGCCCTCTGCCTTCAGCT	AGCTGAAGGCAGAGGGCAC
2065	TGCCCTCTGCCTTCAGCTT	AAGCTGAAGGCAGAGGGCA
2066	GCCCTCTGCCTTCAGCTTA	TAAGCTGAAGGCAGAGGGC
2067	CCCTCTGCCTTCAGCTTAG	CTAAGCTGAAGGCAGAGGG
2068	CCTCTGCCTTCAGCTTAGG	CCTAAGCTGAAGGCAGAGG
2069	CTCTGCCTTCAGCTTAGGC	GCCTAAGCTGAAGGCAGAG
2070	TCTGCCTTCAGCTTAGGCA	TGCCTAAGCTGAAGGCAGA
2071	CTGCCTTCAGCTTAGGCAG	CTGCCTAAGCTGAAGGCAG
2072	TGCCTTCAGCTTAGGCAGC	GCTGCCTAAGCTGAAGGCA
2073	GCCTTCAGCTTAGGCAGCA	TGCTGCCTAAGCTGAAGGC
2074	CCTTCAGCTTAGGCAGCAA	TTGCTGCCTAAGCTGAAGG
2075	CTTCAGCTTAGGCAGCAAG	CTTGCTGCCTAAGCTGAAG
2076	TTCAGCTTAGGCAGCAAGG	CCTTGCTGCCTAAGCTGAA
2077	TCAGCTTAGGCAGCAAGGG	CCCTTGCTGCCTAAGCTGA
2078	CAGCTTAGGCAGCAAGGGC	GCCCTTGCTGCCTAAGCTG
2079	AGCTTAGGCAGCAAGGGCT	AGCCCTTGCTGCCTAAGCT
2080	GCTTAGGCAGCAAGGGCTT	AAGCCCTTGCTGCCTAAGC
2081	CTTAGGCAGCAAGGGCTTT	AAAGCCCTTGCTGCCTAAG
2082	TTAGGCAGCAAGGGCTTTT	AAAAGCCCTTGCTGCCTAA
2083	TAGGCAGCAAGGGCTTTTA	TAAAAGCCCTTGCTGCCTA
2084	AGGCAGCAAGGGCTTTTAC	GTAAAAGCCCTTGCTGCCT
2085	GGCAGCAAGGGCTTTTACT	AGTAAAAGCCCTTGCTGCC
2086	GCAGCAAGGGCTTTTACTA	TAGTAAAAGCCCTTGCTGC
2087	CAGCAAGGGCTTTTACTAC	GTAGTAAAAGCCCTTGCTG
2088	AGCAAGGGCTTTTACTACA	TGTAGTAAAAGCCCTTGCT
2089	GCAAGGGCTTTTACTACAA	TTGTAGTAAAAGCCCTTGC
2090	CAAGGGCTTTTACTACAAG	CTTGTAGTAAAAGCCCTTG
2091	AAGGGCTTTTACTACAAGG	CCTTGTAGTAAAAGCCCTT
2092	AGGGCTTTTACTACAAGGA	TCCTTGTAGTAAAAGCCCT
2093	GGGCTTTTACTACAAGGAT	ATCCTTGTAGTAAAAGCCC
2094	GGCTTTTACTACAAGGATC	GATCCTTGTAGTAAAAGCC
2095	GCTTTTACTACAAGGATCC	GGATCCTTGTAGTAAAAGC
2096	CTTTTACTACAAGGATCCG	CGGATCCTTGTAGTAAAAG
2097	TTTTACTACAAGGATCCGA	TCGGATCCTTGTAGTAAAA
2098	TTTACTACAAGGATCCGAG	CTCGGATCCTTGTAGTAAA
2099	TTACTACAAGGATCCGAGC	GCTCGGATCCTTGTAGTAA
2100	TACTACAAGGATCCGAGCA	TGCTCGGATCCTTGTAGTA
2101	ACTACAAGGATCCGAGCAT	ATGCTCGGATCCTTGTAGT
2102	CTACAAGGATCCGAGCATT	AATGCTCGGATCCTTGTAG
2103	TACAAGGATCCGAGCATTC	GAATGCTCGGATCCTTGTA
2104	ACAAGGATCCGAGCATTCC	GGAATGCTCGGATCCTTGT
2105	CAAGGATCCGAGCATTCCC	GGGAATGCTCGGATCCTTG
2106	AAGGATCCGAGCATTCCCA	TGGGAATGCTCGGATCCTT
2107	AGGATCCGAGCATTCCCAG	CTGGGAATGCTCGGATCCT
2108	GGATCCGAGCATTCCCAGG	CCTGGGAATGCTCGGATCC
2109	GATCCGAGCATTCCCAGGT	ACCTGGGAATGCTCGGATC
2110	ATCCGAGCATTCCCAGGTT	AACCTGGGAATGCTCGGAT
2111	TCCGAGCATTCCCAGGTTG	CAACCTGGGAATGCTCGGA
2112	CCGAGCATTCCCAGGTTGG	CCAACCTGGGAATGCTCGG
2113	CGAGCATTCCCAGGTTGGC	GCCAACCTGGGAATGCTCG
2114	GAGCATTCCCAGGTTGGCA	TGCCAACCTGGGAATGCTC
2115	AGCATTCCCAGGTTGGCAA	TTGCCAACCTGGGAATGCT
2116	GCATTCCCAGGTTGGCAAA	TTTGCCAACCTGGGAATGC
2117	CATTCCCAGGTTGGCAAAG	CTTTGCCAACCTGGGAATG
2118	ATTCCCAGGTTGGCAAAGG	CCTTTGCCAACCTGGGAAT
2119	TTCCCAGGTTGGCAAAGGA	TCCTTTGCCAACCTGGGAA
2120	TCCCAGGTTGGCAAAGGAG	CTCCTTTGCCAACCTGGGA
2121	CCCAGGTTGGCAAAGGAGC	GCTCCTTTGCCAACCTGGG
2122	CCAGGTTGGCAAAGGAGCC	GGCTCCTTTGCCAACCTGG
2123	CAGGTTGGCAAAGGAGCCC	GGGCTCCTTTGCCAACCTG
2124	AGGTTGGCAAAGGAGCCCT	AGGGCTCCTTTGCCAACCT
2125	GGTTGGCAAAGGAGCCCTT	AAGGGCTCCTTTGCCAACC
2126	GTTGGCAAAGGAGCCCTTG	CAAGGGCTCCTTTGCCAAC
2127	TTGGCAAAGGAGCCCTTGG	CCAAGGGCTCCTTTGCCAA
2128	TGGCAAAGGAGCCCTTGGC	GCCAAGGGCTCCTTTGCCA
2129	GGCAAAGGAGCCCTTGGCA	TGCCAAGGGCTCCTTTGCC
2130	GCAAAGGAGCCCTTGGCAG	CTGCCAAGGGCTCCTTTGC
2131	CAAAGGAGCCCTTGGCAGC	GCTGCCAAGGGCTCCTTTG
2132	AAAGGAGCCCTTGGCAGCT	AGCTGCCAAGGGCTCCTTT
2133	AAGGAGCCCTTGGCAGCTG	CAGCTGCCAAGGGCTCCTT
2134	AGGAGCCCTTGGCAGCTGC	GCAGCTGCCAAGGGCTCCT
2135	GGAGCCCTTGGCAGCTGCG	CGCAGCTGCCAAGGGCTCC
2136	GAGCCCTTGGCAGCTGCGG	CCGCAGCTGCCAAGGGCTC
2137	AGCCCTTGGCAGCTGCGGA	TCCGCAGCTGCCAAGGGCT
2138	GCCCTTGGCAGCTGCGGAA	TTCCGCAGCTGCCAAGGGC
2139	CCCTTGGCAGCTGCGGAAC	GTTCCGCAGCTGCCAAGGG
2140	CCTTGGCAGCTGCGGAACC	GGTTCCGCAGCTGCCAAGG
2141	CTTGGCAGCTGCGGAACCT	AGGTTCCGCAGCTGCCAAG
2142	TTGGCAGCTGCGGAACCTG	CAGGTTCCGCAGCTGCCAA
2143	TGGCAGCTGCGGAACCTGG	CCAGGTTCCGCAGCTGCCA
2144	GGCAGCTGCGGAACCTGGG	CCCAGGTTCCGCAGCTGCC
2145	GCAGCTGCGGAACCTGGGT	ACCCAGGTTCCGCAGCTGC
2146	CAGCTGCGGAACCTGGGTT	AACCCAGGTTCCGCAGCTG
2147	AGCTGCGGAACCTGGGTTG	CAACCCAGGTTCCGCAGCT
2148	GCTGCGGAACCTGGGTTGT	ACAACCCAGGTTCCGCAGC
2149	CTGCGGAACCTGGGTTGTT	AACAACCCAGGTTCCGCAG
2150	TGCGGAACCTGGGTTGTTT	AAACAACCCAGGTTCCGCA
2151	GCGGAACCTGGGTTGTTTG	CAAACAACCCAGGTTCCGC
2152	CGGAACCTGGGTTGTTTGG	CCAAACAACCCAGGTTCCG
2153	GGAACCTGGGTTGTTTGGC	GCCAAACAACCCAGGTTCC
2154	GAACCTGGGTTGTTTGGCT	AGCCAAACAACCCAGGTTC
2155	AACCTGGGTTGTTTGGCTT	AAGCCAAACAACCCAGGTT
2156	ACCTGGGTTGTTTGGCTTA	TAAGCCAAACAACCCAGGT
2157	CCTGGGTTGTTTGGCTTAA	TTAAGCCAAACAACCCAGG
2158	CTGGGTTGTTTGGCTTAAA	TTTAAGCCAAACAACCCAG
2159	TGGGTTGTTTGGCTTAAAC	GTTTAAGCCAAACAACCCA
2160	GGGTTGTTTGGCTTAAACT	AGTTTAAGCCAAACAACCC
2161	GGTTGTTTGGCTTAAACTC	GAGTTTAAGCCAAACAACC
2162	GTTGTTTGGCTTAAACTCT	AGAGTTTAAGCCAAACAAC
2163	TTGTTTGGCTTAAACTCTG	CAGAGTTTAAGCCAAACAA
2164	TGTTTGGCTTAAACTCTGG	CCAGAGTTTAAGCCAAACA
2165	GTTTGGCTTAAACTCTGGT	ACCAGAGTTTAAGCCAAAC
2166	TTTGGCTTAAACTCTGGTG	CACCAGAGTTTAAGCCAAA
2167	TTGGCTTAAACTCTGGTGG	CCACCAGAGTTTAAGCCAA
2168	TGGCTTAAACTCTGGTGGG	CCCACCAGAGTTTAAGCCA
2169	GGCTTAAACTCTGGTGGGC	GCCCACCAGAGTTTAAGCC
2170	GCTTAAACTCTGGTGGGCA	TGCCCACCAGAGTTTAAGC
2171	CTTAAACTCTGGTGGGCAC	GTGCCCACCAGAGTTTAAG
2172	TTAAACTCTGGTGGGCACC	GGTGCCCACCAGAGTTTAA
2173	TAAACTCTGGTGGGCACCT	AGGTGCCCACCAGAGTTTA
2174	AAACTCTGGTGGGCACCTG	CAGGTGCCCACCAGAGTTT
2175	AACTCTGGTGGGCACCTGC	GCAGGTGCCCACCAGAGTT
2176	ACTCTGGTGGGCACCTGCA	TGCAGGTGCCCACCAGAGT
2177	CTCTGGTGGGCACCTGCAG	CTGCAGGTGCCCACCAGAG
2178	TCTGGTGGGCACCTGCAGA	TCTGCAGGTGCCCACCAGA
2179	CTGGTGGGCACCTGCAGAG	CTCTGCAGGTGCCCACCAG
2180	TGGTGGGCACCTGCAGAGA	TCTCTGCAGGTGCCCACCA
2181	GGTGGGCACCTGCAGAGAG	CTCTCTGCAGGTGCCCACC
2182	GTGGGCACCTGCAGAGAGC	GCTCTCTGCAGGTGCCCAC
2183	TGGGCACCTGCAGAGAGCC	GGCTCTCTGCAGGTGCCCA
2184	GGGCACCTGCAGAGAGCCG	CGGCTCTCTGCAGGTGCCC
2185	GGCACCTGCAGAGAGCCGG	CCGGCTCTCTGCAGGTGCC
2186	GCACCTGCAGAGAGCCGGG	CCCGGCTCTCTGCAGGTGC
2187	CACCTGCAGAGAGCCGGGG	CCCCGGCTCTCTGCAGGTG
2188	ACCTGCAGAGAGCCGGGGA	TCCCCGGCTCTCTGCAGGT
2189	CCTGCAGAGAGCCGGGGAG	CTCCCCGGCTCTCTGCAGG
2190	CTGCAGAGAGCCGGGGAGG	CCTCCCCGGCTCTCTGCAG
2191	TGCAGAGAGCCGGGGAGGC	GCCTCCCCGGCTCTCTGCA
2192	GCAGAGAGCCGGGGAGGCC	GGCCTCCCCGGCTCTCTGC
2193	CAGAGAGCCGGGGAGGCCG	CGGCCTCCCCGGCTCTCTG
2194	AGAGAGCCGGGGAGGCCGA	TCGGCCTCCCCGGCTCTCT
2195	GAGAGCCGGGGAGGCCGAA	TTCGGCCTCCCCGGCTCTC
2196	AGAGCCGGGGAGGCCGAAC	GTTCGGCCTCCCCGGCTCT
2197	GAGCCGGGGAGGCCGAACG	CGTTCGGCCTCCCCGGCTC
2198	AGCCGGGGAGGCCGAACGC	GCGTTCGGCCTCCCCGGCT
2199	GCCGGGGAGGCCGAACGCC	GGCGTTCGGCCTCCCCGGC
2200	CCGGGGAGGCCGAACGCCC	GGGCGTTCGGCCTCCCCGG
2201	CGGGGAGGCCGAACGCCCT	AGGGCGTTCGGCCTCCCCG
2202	GGGGAGGCCGAACGCCCTT	AAGGGCGTTCGGCCTCCCC
2203	GGGAGGCCGAACGCCCTTC	GAAGGGCGTTCGGCCTCCC
2204	GGAGGCCGAACGCCCTTCA	TGAAGGGCGTTCGGCCTCC
2205	GAGGCCGAACGCCCTTCAC	GTGAAGGGCGTTCGGCCTC
2206	AGGCCGAACGCCCTTCACT	AGTGAAGGGCGTTCGGCCT
2207	GGCCGAACGCCCTTCACTG	CAGTGAAGGGCGTTCGGCC
2208	GCCGAACGCCCTTCACTGC	GCAGTGAAGGGCGTTCGGC
2209	CCGAACGCCCTTCACTGCA	TGCAGTGAAGGGCGTTCGG
2210	CGAACGCCCTTCACTGCAC	GTGCAGTGAAGGGCGTTCG
2211	GAACGCCCTTCACTGCACC	GGTGCAGTGAAGGGCGTTC
2212	AACGCCCTTCACTGCACCA	TGGTGCAGTGAAGGGCGTT
2213	ACGCCCTTCACTGCACCAG	CTGGTGCAGTGAAGGGCGT
2214	CGCCCTTCACTGCACCAGA	TCTGGTGCAGTGAAGGGCG
2215	GCCCTTCACTGCACCAGAG	CTCTGGTGCAGTGAAGGGC
2216	CCCTTCACTGCACCAGAGG	CCTCTGGTGCAGTGAAGGG
2217	CCTTCACTGCACCAGAGGG	CCCTCTGGTGCAGTGAAGG
2218	CTTCACTGCACCAGAGGGA	TCCCTCTGGTGCAGTGAAG
2219	TTCACTGCACCAGAGGGAT	ATCCCTCTGGTGCAGTGAA
2220	TCACTGCACCAGAGGGATG	CATCCCTCTGGTGCAGTGA
2221	CACTGCACCAGAGGGATGG	CCATCCCTCTGGTGCAGTG
2222	ACTGCACCAGAGGGATGGA	TCCATCCCTCTGGTGCAGT
2223	CTGCACCAGAGGGATGGAG	CTCCATCCCTCTGGTGCAG
2224	TGCACCAGAGGGATGGAGA	TCTCCATCCCTCTGGTGCA
2225	GCACCAGAGGGATGGAGAG	CTCTCCATCCCTCTGGTGC
2226	CACCAGAGGGATGGAGAGA	TCTCTCCATCCCTCTGGTG
2227	ACCAGAGGGATGGAGAGAT	ATCTCTCCATCCCTCTGGT
2228	CCAGAGGGATGGAGAGATG	CATCTCTCCATCCCTCTGG
2229	CAGAGGGATGGAGAGATGG	CCATCTCTCCATCCCTCTG
2230	AGAGGGATGGAGAGATGGG	CCCATCTCTCCATCCCTCT
2231	GAGGGATGGAGAGATGGGA	TCCCATCTCTCCATCCCTC
2232	AGGGATGGAGAGATGGGAG	CTCCCATCTCTCCATCCCT
2233	GGGATGGAGAGATGGGAGC	GCTCCCATCTCTCCATCCC
2234	GGATGGAGAGATGGGAGCT	AGCTCCCATCTCTCCATCC
2235	GATGGAGAGATGGGAGCTG	CAGCTCCCATCTCTCCATC
2236	ATGGAGAGATGGGAGCTGG	CCAGCTCCCATCTCTCCAT
2237	TGGAGAGATGGGAGCTGGC	GCCAGCTCCCATCTCTCCA
2238	GGAGAGATGGGAGCTGGCC	GGCCAGCTCCCATCTCTCC
2239	GAGAGATGGGAGCTGGCCG	CGGCCAGCTCCCATCTCTC
2240	AGAGATGGGAGCTGGCCGG	CCGGCCAGCTCCCATCTCT
2241	GAGATGGGAGCTGGCCGGC	GCCGGCCAGCTCCCATCTC
2242	AGATGGGAGCTGGCCGGCA	TGCCGGCCAGCTCCCATCT
2243	GATGGGAGCTGGCCGGCAG	CTGCCGGCCAGCTCCCATC
2244	ATGGGAGCTGGCCGGCAGC	GCTGCCGGCCAGCTCCCAT
2245	TGGGAGCTGGCCGGCAGCA	TGCTGCCGGCCAGCTCCCA
2246	GGGAGCTGGCCGGCAGCAG	CTGCTGCCGGCCAGCTCCC
2247	GGAGCTGGCCGGCAGCAGA	TCTGCTGCCGGCCAGCTCC
2248	GAGCTGGCCGGCAGCAGAA	TTCTGCTGCCGGCCAGCTC
2249	AGCTGGCCGGCAGCAGAAT	ATTCTGCTGCCGGCCAGCT
2250	GCTGGCCGGCAGCAGAATC	GATTCTGCTGCCGGCCAGC
2251	CTGGCCGGCAGCAGAATCC	GGATTCTGCTGCCGGCCAG
2252	TGGCCGGCAGCAGAATCCT	AGGATTCTGCTGCCGGCCA
2253	GGCCGGCAGCAGAATCCTT	AAGGATTCTGCTGCCGGCC
2254	GCCGGCAGCAGAATCCTTG	CAAGGATTCTGCTGCCGGC
2255	CCGGCAGCAGAATCCTTGC	GCAAGGATTCTGCTGCCGG
2256	CGGCAGCAGAATCCTTGCC	GGCAAGGATTCTGCTGCCG
2257	GGCAGCAGAATCCTTGCCC	GGGCAAGGATTCTGCTGCC
2258	GCAGCAGAATCCTTGCCCG	CGGGCAAGGATTCTGCTGC
2259	CAGCAGAATCCTTGCCCGC	GCGGGCAAGGATTCTGCTG
2260	AGCAGAATCCTTGCCCGCT	AGCGGGCAAGGATTCTGCT
2261	GCAGAATCCTTGCCCGCTC	GAGCGGGCAAGGATTCTGC
2262	CAGAATCCTTGCCCGCTCT	AGAGCGGGCAAGGATTCTG
2263	AGAATCCTTGCCCGCTCTT	AAGAGCGGGCAAGGATTCT
2264	GAATCCTTGCCCGCTCTTC	GAAGAGCGGGCAAGGATTC
2265	AATCCTTGCCCGCTCTTCC	GGAAGAGCGGGCAAGGATT
2266	ATCCTTGCCCGCTCTTCCT	AGGAAGAGCGGGCAAGGAT
2267	TCCTTGCCCGCTCTTCCTG	CAGGAAGAGCGGGCAAGGA
2268	CCTTGCCCGCTCTTCCTGG	CCAGGAAGAGCGGGCAAGG
2269	CTTGCCCGCTCTTCCTGGG	CCCAGGAAGAGCGGGCAAG
2270	TTGCCCGCTCTTCCTGGGG	CCCCAGGAAGAGCGGGCAA
2271	TGCCCGCTCTTCCTGGGGC	GCCCCAGGAAGAGCGGGCA
2272	GCCCGCTCTTCCTGGGGCA	TGCCCCAGGAAGAGCGGGC
2273	CCCGCTCTTCCTGGGGCAG	CTGCCCCAGGAAGAGCGGG
2274	CCGCTCTTCCTGGGGCAGC	GCTGCCCCAGGAAGAGCGG
2275	CGCTCTTCCTGGGGCAGCC	GGCTGCCCCAGGAAGAGCG
2276	GCTCTTCCTGGGGCAGCCA	TGGCTGCCCCAGGAAGAGC
2277	CTCTTCCTGGGGCAGCCAG	CTGGCTGCCCCAGGAAGAG
2278	TCTTCCTGGGGCAGCCAGA	TCTGGCTGCCCCAGGAAGA
2279	CTTCCTGGGGCAGCCAGAC	GTCTGGCTGCCCCAGGAAG
2280	TTCCTGGGGCAGCCAGACA	TGTCTGGCTGCCCCAGGAA
2281	TCCTGGGGCAGCCAGACAC	GTGTCTGGCTGCCCCAGGA
2282	CCTGGGGCAGCCAGACACT	AGTGTCTGGCTGCCCCAGG
2283	CTGGGGCAGCCAGACACTG	CAGTGTCTGGCTGCCCCAG
2284	TGGGGCAGCCAGACACTGT	ACAGTGTCTGGCTGCCCCA
2285	GGGGCAGCCAGACACTGTG	CACAGTGTCTGGCTGCCCC
2286	GGGCAGCCAGACACTGTGC	GCACAGTGTCTGGCTGCCC
2287	GGCAGCCAGACACTGTGCC	GGCACAGTGTCTGGCTGCC
2288	GCAGCCAGACACTGTGCCC	GGGCACAGTGTCTGGCTGC
2289	CAGCCAGACACTGTGCCCT	AGGGCACAGTGTCTGGCTG
2290	AGCCAGACACTGTGCCCTG	CAGGGCACAGTGTCTGGCT
2291	GCCAGACACTGTGCCCTGG	CCAGGGCACAGTGTCTGGC
2292	CCAGACACTGTGCCCTGGA	TCCAGGGCACAGTGTCTGG
2293	CAGACACTGTGCCCTGGAC	GTCCAGGGCACAGTGTCTG
2294	AGACACTGTGCCCTGGACC	GGTCCAGGGCACAGTGTCT
2295	GACACTGTGCCCTGGACCT	AGGTCCAGGGCACAGTGTC
2296	ACACTGTGCCCTGGACCTC	GAGGTCCAGGGCACAGTGT
2297	CACTGTGCCCTGGACCTCC	GGAGGTCCAGGGCACAGTG
2298	ACTGTGCCCTGGACCTCCT	AGGAGGTCCAGGGCACAGT
2299	CTGTGCCCTGGACCTCCTG	CAGGAGGTCCAGGGCACAG
2300	TGTGCCCTGGACCTCCTGG	CCAGGAGGTCCAGGGCACA
2301	GTGCCCTGGACCTCCTGGC	GCCAGGAGGTCCAGGGCAC
2302	TGCCCTGGACCTCCTGGCC	GGCCAGGAGGTCCAGGGCA
2303	GCCCTGGACCTCCTGGCCC	GGGCCAGGAGGTCCAGGGC
2304	CCCTGGACCTCCTGGCCCG	CGGGCCAGGAGGTCCAGGG
2305	CCTGGACCTCCTGGCCCGC	GCGGGCCAGGAGGTCCAGG
2306	CTGGACCTCCTGGCCCGCT	AGCGGGCCAGGAGGTCCAG
2307	TGGACCTCCTGGCCCGCTT	AAGCGGGCCAGGAGGTCCA
2308	GGACCTCCTGGCCCGCTTG	CAAGCGGGCCAGGAGGTCC
2309	GACCTCCTGGCCCGCTTGT	ACAAGCGGGCCAGGAGGTC
2310	ACCTCCTGGCCCGCTTGTC	GACAAGCGGGCCAGGAGGT
2311	CCTCCTGGCCCGCTTGTCC	GGACAAGCGGGCCAGGAGG
2312	CTCCTGGCCCGCTTGTCCC	GGGACAAGCGGGCCAGGAG
2313	TCCTGGCCCGCTTGTCCCC	GGGGACAAGCGGGCCAGGA
2314	CCTGGCCCGCTTGTCCCCC	GGGGGACAAGCGGGCCAGG
2315	CTGGCCCGCTTGTCCCCCA	TGGGGGACAAGCGGGCCAG
2316	TGGCCCGCTTGTCCCCCAG	CTGGGGGACAAGCGGGCCA
2317	GGCCCGCTTGTCCCCCAGG	CCTGGGGGACAAGCGGGCC
2318	GCCCGCTTGTCCCCCAGGC	GCCTGGGGGACAAGCGGGC
2319	CCCGCTTGTCCCCCAGGCC	GGCCTGGGGGACAAGCGGG
2320	CCGCTTGTCCCCCAGGCCT	AGGCCTGGGGGACAAGCGG
2321	CGCTTGTCCCCCAGGCCTT	AAGGCCTGGGGGACAAGCG
2322	GCTTGTCCCCCAGGCCTTG	CAAGGCCTGGGGGACAAGC
2323	CTTGTCCCCCAGGCCTTGT	ACAAGGCCTGGGGGACAAG
2324	TTGTCCCCCAGGCCTTGTT	AACAAGGCCTGGGGGACAA
2325	TGTCCCCCAGGCCTTGTTC	GAACAAGGCCTGGGGGACA
2326	GTCCCCCAGGCCTTGTTCA	TGAACAAGGCCTGGGGGAC
2327	TCCCCCAGGCCTTGTTCAT	ATGAACAAGGCCTGGGGGA
2328	CCCCCAGGCCTTGTTCATA	TATGAACAAGGCCTGGGGG
2329	CCCCAGGCCTTGTTCATAC	GTATGAACAAGGCCTGGGG
2330	CCCAGGCCTTGTTCATACT	AGTATGAACAAGGCCTGGG
2331	CCAGGCCTTGTTCATACTC	GAGTATGAACAAGGCCTGG
2332	CAGGCCTTGTTCATACTCT	AGAGTATGAACAAGGCCTG
2333	AGGCCTTGTTCATACTCTT	AAGAGTATGAACAAGGCCT
2334	GGCCTTGTTCATACTCTTG	CAAGAGTATGAACAAGGCC
2335	GCCTTGTTCATACTCTTGG	CCAAGAGTATGAACAAGGC
2336	CCTTGTTCATACTCTTGGC	GCCAAGAGTATGAACAAGG
2337	CTTGTTCATACTCTTGGCA	TGCCAAGAGTATGAACAAG
2338	TTGTTCATACTCTTGGCAA	TTGCCAAGAGTATGAACAA
2339	TGTTCATACTCTTGGCAAC	GTTGCCAAGAGTATGAACA
2340	GTTCATACTCTTGGCAACG	CGTTGCCAAGAGTATGAAC
2341	TTCATACTCTTGGCAACGT	ACGTTGCCAAGAGTATGAA
2342	TCATACTCTTGGCAACGTC	GACGTTGCCAAGAGTATGA
2343	CATACTCTTGGCAACGTCT	AGACGTTGCCAAGAGTATG
2344	ATACTCTTGGCAACGTCTG	CAGACGTTGCCAAGAGTAT
2345	TACTCTTGGCAACGTCTGG	CCAGACGTTGCCAAGAGTA
2346	ACTCTTGGCAACGTCTGGG	CCCAGACGTTGCCAAGAGT
2347	CTCTTGGCAACGTCTGGGC	GCCCAGACGTTGCCAAGAG
2348	TCTTGGCAACGTCTGGGCT	AGCCCAGACGTTGCCAAGA
2349	CTTGGCAACGTCTGGGCTG	CAGCCCAGACGTTGCCAAG
2350	TTGGCAACGTCTGGGCTGG	CCAGCCCAGACGTTGCCAA
2351	TGGCAACGTCTGGGCTGGG	CCCAGCCCAGACGTTGCCA
2352	GGCAACGTCTGGGCTGGGC	GCCCAGCCCAGACGTTGCC
2353	GCAACGTCTGGGCTGGGCC	GGCCCAGCCCAGACGTTGC
2354	CAACGTCTGGGCTGGGCCA	TGGCCCAGCCCAGACGTTG
2355	AACGTCTGGGCTGGGCCAG	CTGGCCCAGCCCAGACGTT
2356	ACGTCTGGGCTGGGCCAGG	CCTGGCCCAGCCCAGACGT
2357	CGTCTGGGCTGGGCCAGGC	GCCTGGCCCAGCCCAGACG
2358	GTCTGGGCTGGGCCAGGCG	CGCCTGGCCCAGCCCAGAC
2359	TCTGGGCTGGGCCAGGCGA	TCGCCTGGCCCAGCCCAGA
2360	CTGGGCTGGGCCAGGCGAT	ATCGCCTGGCCCAGCCCAG
2361	TGGGCTGGGCCAGGCGATG	CATCGCCTGGCCCAGCCCA
2362	GGGCTGGGCCAGGCGATGG	CCATCGCCTGGCCCAGCCC
2363	GGCTGGGCCAGGCGATGGG	CCCATCGCCTGGCCCAGCC
2364	GCTGGGCCAGGCGATGGGA	TCCCATCGCCTGGCCCAGC
2365	CTGGGCCAGGCGATGGGAA	TTCCCATCGCCTGGCCCAG
2366	TGGGCCAGGCGATGGGAAC	GTTCCCATCGCCTGGCCCA
2367	GGGCCAGGCGATGGGAACC	GGTTCCCATCGCCTGGCCC
2368	GGCCAGGCGATGGGAACCT	AGGTTCCCATCGCCTGGCC
2369	GCCAGGCGATGGGAACCTT	AAGGTTCCCATCGCCTGGC
2370	CCAGGCGATGGGAACCTTG	CAAGGTTCCCATCGCCTGG
2371	CAGGCGATGGGAACCTTGG	CCAAGGTTCCCATCGCCTG
2372	AGGCGATGGGAACCTTGGG	CCCAAGGTTCCCATCGCCT
2373	GGCGATGGGAACCTTGGGT	ACCCAAGGTTCCCATCGCC
2374	GCGATGGGAACCTTGGGTA	TACCCAAGGTTCCCATCGC
2375	CGATGGGAACCTTGGGTAC	GTACCCAAGGTTCCCATCG
2376	GATGGGAACCTTGGGTACC	GGTACCCAAGGTTCCCATC
2377	ATGGGAACCTTGGGTACCA	TGGTACCCAAGGTTCCCAT
2378	TGGGAACCTTGGGTACCAG	CTGGTACCCAAGGTTCCCA
2379	GGGAACCTTGGGTACCAGC	GCTGGTACCCAAGGTTCCC
2380	GGAACCTTGGGTACCAGCT	AGCTGGTACCCAAGGTTCC
2381	GAACCTTGGGTACCAGCTG	CAGCTGGTACCCAAGGTTC
2382	AACCTTGGGTACCAGCTGG	CCAGCTGGTACCCAAGGTT
2383	ACCTTGGGTACCAGCTGGG	CCCAGCTGGTACCCAAGGT
2384	CCTTGGGTACCAGCTGGGG	CCCCAGCTGGTACCCAAGG
2385	CTTGGGTACCAGCTGGGGC	GCCCCAGCTGGTACCCAAG
2386	TTGGGTACCAGCTGGGGCC	GGCCCCAGCTGGTACCCAA
2387	TGGGTACCAGCTGGGGCCA	TGGCCCCAGCTGGTACCCA
2388	GGGTACCAGCTGGGGCCAC	GTGGCCCCAGCTGGTACCC
2389	GGTACCAGCTGGGGCCACC	GGTGGCCCCAGCTGGTACC
2390	GTACCAGCTGGGGCCACCA	TGGTGGCCCCAGCTGGTAC
2391	TACCAGCTGGGGCCACCAG	CTGGTGGCCCCAGCTGGTA
2392	ACCAGCTGGGGCCACCAGC	GCTGGTGGCCCCAGCTGGT
2393	CCAGCTGGGGCCACCAGCA	TGCTGGTGGCCCCAGCTGG
2394	CAGCTGGGGCCACCAGCAA	TTGCTGGTGGCCCCAGCTG
2395	AGCTGGGGCCACCAGCAAC	GTTGCTGGTGGCCCCAGCT
2396	GCTGGGGCCACCAGCAACA	TGTTGCTGGTGGCCCCAGC
2397	CTGGGGCCACCAGCAACAC	GTGTTGCTGGTGGCCCCAG
2398	TGGGGCCACCAGCAACACC	GGTGTTGCTGGTGGCCCCA
2399	GGGGCCACCAGCAACACCA	TGGTGTTGCTGGTGGCCCC
2400	GGGCCACCAGCAACACCAA	TTGGTGTTGCTGGTGGCCC
2401	GGCCACCAGCAACACCAAG	CTTGGTGTTGCTGGTGGCC
2402	GCCACCAGCAACACCAAGG	CCTTGGTGTTGCTGGTGGC
2403	CCACCAGCAACACCAAGGT	ACCTTGGTGTTGCTGGTGG
2404	CACCAGCAACACCAAGGTG	CACCTTGGTGTTGCTGGTG
2405	ACCAGCAACACCAAGGTGC	GCACCTTGGTGTTGCTGGT
2406	CCAGCAACACCAAGGTGCC	GGCACCTTGGTGTTGCTGG
2407	CAGCAACACCAAGGTGCCC	GGGCACCTTGGTGTTGCTG
2408	AGCAACACCAAGGTGCCCC	GGGGCACCTTGGTGTTGCT
2409	GCAACACCAAGGTGCCCCT	AGGGGCACCTTGGTGTTGC
2410	CAACACCAAGGTGCCCCTC	GAGGGGCACCTTGGTGTTG
2411	AACACCAAGGTGCCCCTCT	AGAGGGGCACCTTGGTGTT
2412	ACACCAAGGTGCCCCTCTC	GAGAGGGGCACCTTGGTGT
2413	CACCAAGGTGCCCCTCTCC	GGAGAGGGGCACCTTGGTG
2414	ACCAAGGTGCCCCTCTCCT	AGGAGAGGGGCACCTTGGT
2415	CCAAGGTGCCCCTCTCCTG	CAGGAGAGGGGCACCTTGG
2416	CAAGGTGCCCCTCTCCTGA	TCAGGAGAGGGGCACCTTG
2417	AAGGTGCCCCTCTCCTGAG	CTCAGGAGAGGGGCACCTT
2418	AGGTGCCCCTCTCCTGAGC	GCTCAGGAGAGGGGCACCT
2419	GGTGCCCCTCTCCTGAGCC	GGCTCAGGAGAGGGGCACC
2420	GTGCCCCTCTCCTGAGCCG	CGGCTCAGGAGAGGGGCAC
2421	TGCCCCTCTCCTGAGCCGC	GCGGCTCAGGAGAGGGGCA
2422	GCCCCTCTCCTGAGCCGCC	GGCGGCTCAGGAGAGGGGC
2423	CCCCTCTCCTGAGCCGCCT	AGGCGGCTCAGGAGAGGGG
2424	CCCTCTCCTGAGCCGCCTG	CAGGCGGCTCAGGAGAGGG
2425	CCTCTCCTGAGCCGCCTGT	ACAGGCGGCTCAGGAGAGG
2426	CTCTCCTGAGCCGCCTGTC	GACAGGCGGCTCAGGAGAG
2427	TCTCCTGAGCCGCCTGTCA	TGACAGGCGGCTCAGGAGA
2428	CTCCTGAGCCGCCTGTCAC	GTGACAGGCGGCTCAGGAG
2429	TCCTGAGCCGCCTGTCACC	GGTGACAGGCGGCTCAGGA
2430	CCTGAGCCGCCTGTCACCC	GGGTGACAGGCGGCTCAGG
2431	CTGAGCCGCCTGTCACCCA	TGGGTGACAGGCGGCTCAG
2432	TGAGCCGCCTGTCACCCAG	CTGGGTGACAGGCGGCTCA
2433	GAGCCGCCTGTCACCCAGC	GCTGGGTGACAGGCGGCTC
2434	AGCCGCCTGTCACCCAGCG	CGCTGGGTGACAGGCGGCT
2435	GCCGCCTGTCACCCAGCGG	CCGCTGGGTGACAGGCGGC
2436	CCGCCTGTCACCCAGCGGG	CCCGCTGGGTGACAGGCGG
2437	CGCCTGTCACCCAGCGGGG	CCCCGCTGGGTGACAGGCG
2438	GCCTGTCACCCAGCGGGGC	GCCCCGCTGGGTGACAGGC
2439	CCTGTCACCCAGCGGGGCT	AGCCCCGCTGGGTGACAGG
2440	CTGTCACCCAGCGGGGCTG	CAGCCCCGCTGGGTGACAG
2441	TGTCACCCAGCGGGGCTGC	GCAGCCCCGCTGGGTGACA
2442	GTCACCCAGCGGGGCTGCT	AGCAGCCCCGCTGGGTGAC
2443	TCACCCAGCGGGGCTGCTG	CAGCAGCCCCGCTGGGTGA
2444	CACCCAGCGGGGCTGCTGT	ACAGCAGCCCCGCTGGGTG
2445	ACCCAGCGGGGCTGCTGTT	AACAGCAGCCCCGCTGGGT
2446	CCCAGCGGGGCTGCTGTTC	GAACAGCAGCCCCGCTGGG
2447	CCAGCGGGGCTGCTGTTCA	TGAACAGCAGCCCCGCTGG
2448	CAGCGGGGCTGCTGTTCAT	ATGAACAGCAGCCCCGCTG
2449	AGCGGGGCTGCTGTTCATC	GATGAACAGCAGCCCCGCT
2450	GCGGGGCTGCTGTTCATCC	GGATGAACAGCAGCCCCGC
2451	CGGGGCTGCTGTTCATCCT	AGGATGAACAGCAGCCCCG
2452	GGGGCTGCTGTTCATCCTA	TAGGATGAACAGCAGCCCC
2453	GGGCTGCTGTTCATCCTAC	GTAGGATGAACAGCAGCCC
2454	GGCTGCTGTTCATCCTACC	GGTAGGATGAACAGCAGCC
2455	GCTGCTGTTCATCCTACCC	GGGTAGGATGAACAGCAGC
2456	CTGCTGTTCATCCTACCCA	TGGGTAGGATGAACAGCAG
2457	TGCTGTTCATCCTACCCAC	GTGGGTAGGATGAACAGCA
2458	GCTGTTCATCCTACCCACC	GGTGGGTAGGATGAACAGC
2459	CTGTTCATCCTACCCACCC	GGGTCGGTAGGATGAACAG
2460	TGTTCATCCTACCCACCCA	TGGGTGGGTAGGATGAACA
2461	GTTCATCCTACCCACCCAC	GTGGGTGGGTAGGATGAAC
2462	TTCATCCTACCCACCCACT	AGTGGGTGGGTAGGATGAA
2463	TCATCCTACCCACCCACTA	TAGTGGGTGGGTAGGATGA
2464	CATCCTACCCACCCACTAA	TTAGTGGGTGGGTAGGATG
2465	ATCCTACCCACCCACTAAA	TTTAGTGGGTGGGTAGGAT
2466	TCCTACCCACCCACTAAAG	CTTTAGTGGGTGGGTAGGA
2467	CCTACCCACCCACTAAAGG	CCTTTAGTGGGTGGGTAGG
2468	CTACCCACCCACTAAAGGT	ACCTTTAGTGGGTGGGTAG
2469	TACCCACCCACTAAAGGTG	CACCTTTAGTGGGTGGGTA
2470	ACCCACCCACTAAAGGTGG	CCACCTTTAGTGGGTGGGT
2471	CCCACCCACTAAAGGTGGG	CCCACCTTTAGTGGGTGGG
2472	CCACCCACTAAAGGTGGGG	CCCCACCTTTAGTGGGTGG
2473	CACCCACTAAAGGTGGGGG	CCCCCACCTTTAGTGGGTG
2474	ACCCACTAAAGGTGGGGGT	ACCCCCACCTTTAGTGGGT
2475	CCCACTAAAGGTGGGGGTC	GACCCCCACCTTTAGTGGG
2476	CCACTAAAGGTGGGGGTCT	AGACCCCCACCTTTAGTGG
2477	CACTAAAGGTGGGGGTCTT	AAGACCCCCACCTTTAGTG
2478	ACTAAAGGTGGGGGTCTTG	CAAGACCCCCACCTTTAGT
2479	CTAAAGGTGGGGGTCTTGG	CCAAGACCCCCACCTTTAG
2480	TAAAGGTGGGGGTCTTGGC	GCCAAGACCCCCACCTTTA
2481	AAAGGTGGGGGTCTTGGCC	GGCCAAGACCCCCACCTTT
2482	AAGGTGGGGGTCTTGGCCC	GGGCCAAGACCCCCACCTT
2483	AGGTGGGGGTCTTGGCCCT	AGGGCCAAGACCCCCACCT
2484	GGTGGGGGTCTTGGCCCTT	AAGGGCCAAGACCCCCACC
2485	GTGGGGGTCTTGGCCCTTG	CAAGGGCCAAGACCCCCAC
2486	TGGGGGTCTTGGCCCTTGT	ACAAGGGCCAAGACCCCCA
2487	GGGGGTCTTGGCCCTTGTG	CACAAGGGCCAAGACCCCC
2488	GGGGTCTTGGCCCTTGTGG	CCACAAGGGCCAAGACCCC
2489	GGGTCTTGGCCCTTGTGGG	CCCACAAGGGCCAAGACCC
2490	GGTCTTGGCCCTTGTGGGA	TCCCACAAGGGCCAAGACC
2491	GTCTTGGCCCTTGTGGGAA	TTCCCACAAGGGCCAAGAC
2492	TCTTGGCCCTTGTGGGAAG	CTTCCCACAAGGGCCAAGA
2493	CTTGGCCCTTGTGGGAAGT	ACTTCCCACAAGGGCCAAG
2494	TTGGCCCTTGTGGGAAGTG	CACTTCCCACAAGGGCCAA
2495	TGGCCCTTGTGGGAAGTGC	GCACTTCCCACAAGGGCCA
2496	GGCCCTTGTGGGAAGTGCC	GGCACTTCCCACAAGGGCC
2497	GCCCTTGTGGGAAGTGCCA	TGGCACTTCCCACAAGGGC
2498	CCCTTGTGGGAAGTGCCAG	CTGGCACTTCCCACAAGGG
2499	CCTTGTGGGAAGTGCCAGG	CCTGGCACTTCCCACAAGG
2500	CTTGTGGGAAGTGCCAGGA	TCCTGGCACTTCCCACAAG
2501	TTGTGGGAAGTGCCAGGAG	CTCCTGGCACTTCCCACAA
2502	TGTGGGAAGTGCCAGGAGG	CCTCCTGGCACTTCCCACA
2503	GTGGGAAGTGCCAGGAGGG	CCCTCCTGGCACTTCCCAC
2504	TGGGAAGTGCCAGGAGGGC	GCCCTCCTGGCACTTCCCA
2505	GGGAAGTGCCAGGAGGGCC	GGCCCTCCTGGCACTTCCC
2506	GGAAGTGCCAGGAGGGCCT	AGGCCCTCCTGGCACTTCC
2507	GAAGTGCCAGGAGGGCCTG	CAGGCCCTCCTGGCACTTC
2508	AAGTGCCAGGAGGGCCTGG	CCAGGCCCTCCTGGCACTT
2509	AGTGCCAGGAGGGCCTGGA	TCCAGGCCCTCCTGGCACT
2510	GTGCCAGGAGGGCCTGGAG	CTCCAGGCCCTCCTGGCAC
2511	TGCCAGGAGGGCCTGGAGG	CCTCCAGGCCCTCCTGGCA
2512	GCCAGGAGGGCCTGGAGGG	CCCTCCAGGCCCTCCTGGC
2513	CCAGGAGGGCCTGGAGGGG	CCCCTCCAGGCCCTCCTGG
2514	CAGGAGGGCCTGGAGGGGG	CCCCCTCCAGGCCCTCCTG
2515	AGGAGGGCCTGGAGGGGGG	CCCCCCTCCAGGCCCTCCT
2516	GGAGGGCCTGGAGGGGGGT	ACCCCCCTCCAGGCCCTCC
2517	GAGGGCCTGGAGGGGGGTG	CACCCCCCTCCAGGCCCTC
2518	AGGGCCTGGAGGGGGGTGC	GCACCCCCCTCCAGGCCCT
2519	GGGCCTGGAGGGGGGTGCC	GGCACCCCCCTCCAGGCCC
2520	GGCCTGGAGGGGGGTGCCA	TGGCACCCCCCTCCAGGCC
2521	GCCTGGAGGGGGGTGCCAG	CTGGCACCCCCCTCCAGGC
2522	CCTGGAGGGGGGTGCCAGT	ACTGGCACCCCCCTCCAGG
2523	CTGGAGGGGGGTGCCAGTG	CACTGGCACCCCCCTCCAG
2524	TGGAGGGGGGTGCCAGTGG	CCACTGGCACCCCCCTCCA
2525	GGAGGGGGGTGCCAGTGGA	TCCACTGGCACCCCCCTCC
2526	GAGGGGGGTGCCAGTGGAG	CTCCACTGGCACCCCCCTC
2527	AGGGGGGTGCCAGTGGAGC	GCTCCACTGGCACCCCCCT
2528	GGGGGGTGCCAGTGGAGCC	GGCTCCACTGGCACCCCCC
2529	GGGGGTGCCAGTGGAGCCA	TGGCTCCACTGGCACCCCC
2530	GGGGTGCCAGTGGAGCCAG	CTGGCTCCACTGGCACCCC
2531	GGGTGCCAGTGGAGCCAGC	GCTGGCTCCACTGGCACCC
2532	GGTGCCAGTGGAGCCAGCG	CGCTGGCTCCACTGGCACC
2533	GTGCCAGTGGAGCCAGCGA	TCGCTGGCTCCACTGGCAC
2534	TGCCAGTGGAGCCAGCGAA	TTCGCTGGCTCCACTGGCA
2535	GCCAGTGGAGCCAGCGAAC	GTTCGCTGGCTCCACTGGC
2536	CCAGTGGAGCCAGCGAACC	GGTTCGCTGGCTCCACTGG
2537	CAGTGGAGCCAGCGAACCC	GGGTTCGCTGGCTCCACTG
2538	AGTGGAGCCAGCGAACCCA	TGGGTTCGCTGGCTCCACT
2539	GTGGAGCCAGCGAACCCAG	CTGGGTTCGCTGGCTCCAC
2540	TGGAGCCAGCGAACCCAGC	GCTGGGTTCGCTGGCTCCA
2541	GGAGCCAGCGAACCCAGCG	CGCTGGGTTCGCTGGCTCC
2542	GAGCCAGCGAACCCAGCGA	TCGCTGGGTTCGCTGGCTC
2543	AGCCAGCGAACCCAGCGAG	CTCGCTGGGTTCGCTGGCT
2544	GCCAGCGAACCCAGCGAGG	CCTCGCTGGGTTCGCTGGC
2545	CCAGCGAACCCAGCGAGGA	TCCTCGCTGGGTTCGCTGG
2546	CAGCGAACCCAGCGAGGAA	TTCCTCGCTGGGTTCGCTG
2547	AGCGAACCCAGCGAGGAAG	CTTCCTCGCTGGGTTCGCT
2548	GCGAACCCAGCGAGGAAGT	ACTTCCTCGCTGGGTTCGC
2549	CGAACCCAGCGAGGAAGTG	CACTTCCTCGCTGGGTTCG
2550	GAACCCAGCGAGGAAGTGA	TCACTTCCTCGCTGGGTTC
2551	AACCCAGCGAGGAAGTGAA	TTCACTTCCTCGCTGGGTT
2552	ACCCAGCGAGGAAGTGAAC	GTTCACTTCCTCGCTGGGT
2553	CCCAGCGAGGAAGTGAACA	TGTTCACTTCCTCGCTGGG
2554	CCAGCGAGGAAGTGAACAA	TTGTTCACTTCCTCGCTGG
2555	CAGCGAGGAAGTGAACAAG	CTTGTTCACTTCCTCGCTG
2556	AGCGAGGAAGTGAACAAGG	CCTTGTTCACTTCCTCGCT
2557	GCGAGGAAGTGAACAAGGC	GCCTTGTTCACTTCCTCGC
2558	CGAGGAAGTGAACAAGGCC	GGCCTTGTTCACTTCCTCG
2559	GAGGAAGTGAACAAGGCCT	AGGCCTTGTTCACTTCCTC
2560	AGGAAGTGAACAAGGCCTC	GAGGCCTTGTTCACTTCCT
2561	GGAAGTGAACAAGGCCTCT	AGAGGCCTTGTTCACTTCC
2562	GAAGTGAACAAGGCCTCTG	CAGAGGCCTTGTTCACTTC
2563	AAGTGAACAAGGCCTCTGG	CCAGAGGCCTTGTTCACTT
2564	AGTGAACAAGGCCTCTGGC	GCCAGAGGCCTTGTTCACT
2565	GTGAACAAGGCCTCTGGCC	GGCCAGAGGCCTTGTTCAC
2566	TGAACAAGGCCTCTGGCCC	GGGCCAGAGGCCTTGTTCA
2567	GAACAAGGCCTCTGGCCCC	GGGGCCAGAGGCCTTGTTC
2568	AACAAGGCCTCTGGCCCCA	TGGGGCCAGAGGCCTTGTT
2569	ACAAGGCCTCTGGCCCCAG	CTGGGGCCAGAGGCCTTGT
2570	CAAGGCCTCTGGCCCCAGG	CCTGGGGCCAGAGGCCTTG
2571	AAGGCCTCTGGCCCCAGGG	CCCTGGGGCCAGAGGCCTT
2572	AGGCCTCTGGCCCCAGGGC	GCCCTGGGGCCAGAGGCCT
2573	GGCCTCTGGCCCCAGGGCC	GGCCCTGGGGCCAGAGGCC
2574	GCCTCTGGCCCCAGGGCCT	AGGCCCTGGGGCCAGAGGC
2575	CCTCTGGCCCCAGGGCCTG	CAGGCCCTGGGGCCAGAGG
2576	CTCTGGCCCCAGGGCCTGT	ACAGGCCCTGGGGCCAGAG
2577	TCTGGCCCCAGGGCCTGTC	GACAGGCCCTGGGGCCAGA
2578	CTGGCCCCAGGGCCTGTCC	GGACAGGCCCTGGGGCCAG
2579	TGGCCCCAGGGCCTGTCCC	GGGACAGGCCCTGGGGCCA
2580	GGCCCCAGGGCCTGTCCCC	GGGGACAGGCCCTGGGGCC
2581	GCCCCAGGGCCTGTCCCCC	GGGGGACAGGCCCTGGGGC
2582	CCCCAGGGCCTGTCCCCCC	GGGGGGACAGGCCCTGGGG
2583	CCCAGGGCCTGTCCCCCCA	TGGGGGGACAGGCCCTGGG
2584	CCAGGGCCTGTCCCCCCAG	CTGGGGGGACAGGCCCTGG
2585	CAGGGCCTGTCCCCCCAGC	GCTGGGGGGACAGGCCCTG
2586	AGGGCCTGTCGCCCCAGCC	GGCTGGGGGGACAGGCCCT
2587	GGGCCTGTCCGCCCAGCCA	TGGCTGGGGGGACAGGCCC
2588	GGCCTGTCCCCCCAGCCAC	GTGGCTGGGGGGACAGGCC
2589	GCCTGTCCCCCCAGCCACC	GGTGGCTGGGGGGACAGGC
2590	CCTGTCCCCCCAGCCACCA	TGGTGGCTGGGGGGACAGG
2591	CTGTCCCCCCAGCGACCAC	GTGGTGGCTGGGGGGACAG
2592	TGTCCCCCCAGCCACCACA	TGTGGTGGCTGGGGGGACA
2593	GTCCCCCCAGCCACCACAC	GTGTGGTGGCTGGGGGGAC
2594	TCCCCCCAGCCACCACACC	GGTGTGGTGGCTGGGGGGA
2595	CCCCCCAGCCACCACACCA	TGGTGTGGTGGCTGGGGGG
2596	CCCCCAGCCACCACACCAA	TTGGTGTGGTGGCTGGGGG
2597	CCCCAGCCACCACACCAAG	CTTGGTGTGGTGGCTGGGG
2598	CCCAGCCACCACACCAAGC	GCTTGGTGTGGTGGCTGGG
2599	CCAGCCACCACACCAAGCT	AGCTTGGTGTGGTGGCTGG
2600	CAGCCACCACACCAAGCTG	CAGCTTGGTGTGGTGGCTG
2601	AGCCACCACACCAAGCTGA	TCAGCTTGGTGTGGTGGCT
2602	GCCACCACACCAAGCTGAA	TTCAGCTTGGTGTGGTGGC
2603	CCACCACACCAAGCTGAAG	CTTCAGCTTGGTGTGGTGG
2604	CACCACACCAAGCTGAAGA	TCTTCAGCTTGGTGTGGTG
2605	ACCACACCAAGCTGAAGAA	TTCTTCAGCTTGGTGTGGT
2606	CCACACCAAGCTGAAGAAG	CTTCTTCAGCTTGGTGTGG
2607	CACACCAAGCTGAAGAAGA	TCTTCTTCAGCTTGGTGTG
2608	ACACCAAGCTGAAGAAGAC	GTCTTCTTCAGCTTGGTGT
2609	CACCAAGCTGAAGAAGACA	TGTCTTCTTCAGCTTGGTG
2610	ACCAAGCTGAAGAAGACAT	ATGTCTTCTTCAGCTTGGT
2611	CCAAGCTGAAGAAGACATG	CATGTCTTCTTCAGCTTGG
2612	CAAGCTGAAGAAGACATGG	CCATGTCTTCTTCAGCTTG
2613	AAGCTGAAGAAGACATGGC	GCCATGTCTTCTTCAGCTT
2614	AGCTGAAGAAGACATGGCT	AGCCATGTCTTCTTCAGCT
2615	GCTGAAGAAGACATGGCTC	GAGCCATGTCTTCTTCAGC
2616	CTGAAGAAGACATGGCTCA	TGAGCCATGTCTTCTTCAG
2617	TGAAGAAGACATGGCTCAC	GTGAGCCATGTCTTCTTCA
2618	GAAGAAGACATGGCTCACA	TGTGAGCCATGTCTTCTTC
2619	AAGAAGACATGGCTCACAC	GTGTGAGCCATGTCTTCTT
2620	AGAAGACATGGCTCACACG	CGTGTGAGCCATGTCTTCT
2621	GAAGACATGGCTCACACGG	CCGTGTGAGCCATGTCTTC
2622	AAGACATGGCTCACACGGC	GCCGTGTGAGCCATGTCTT
2623	AGACATGGCTCACACGGCA	TGCCGTGTGAGCCATGTCT
2624	GACATGGCTCACACGGCAC	GTGCCGTGTGAGCCATGTC
2625	ACATGGCTCACACGGCACT	AGTGCCGTGTGAGCCATGT
2626	CATGGCTCACACGGCACTC	GAGTGCCGTGTGAGCCATG
2627	ATGGCTCACACGGCACTCG	CGAGTGCCGTGTGAGCCAT
2628	TGGCTCACACGGCACTCGG	CCGAGTGCCGTGTGAGCCA
2629	GGCTCACACGGCACTCGGA	TCCGAGTGCCGTGTGAGCC
2630	GCTCACACGGCACTCGGAG	CTCCGAGTGCCGTGTGAGC
2631	CTCACACGGCACTCGGAGC	GCTCCGAGTGCCGTGTGAG
2632	TCACACGGCACTCGGAGCA	TGCTCCGAGTGCCGTGTGA
2633	CACACGGCACTCGGAGCAG	CTGCTCCGAGTGCCGTGTG
2634	ACACGGCACTCGGAGCAGT	ACTGCTCCGAGTGCCGTGT
2635	CACGGCACTCGGAGCAGTT	AACTGCTCCGAGTGCCGTG
2636	ACGGCACTCGGAGCAGTTT	AAACTGCTCCGAGTGCCGT
2637	CGGCACTCGGAGCAGTTTG	CAAACTGCTCCGAGTGCCG
2638	GGCACTCGGAGCAGTTTGA	TCAAACTGCTCCGAGTGCC
2639	GCACTCGGAGCAGTTTGAA	TTCAAACTGCTCCGAGTGC
2640	CACTCGGAGCAGTTTGAAT	ATTCAAACTGCTCCGAGTG
2641	ACTCGGAGCAGTTTGAATG	CATTCAAACTGCTCCGAGT
2642	CTCGGAGCAGTTTGAATGT	ACATTCAAACTGCTCCGAG
2643	TCGGAGCAGTTTGAATGTC	GACATTCAAACTGCTCCGA
2644	CGGAGCAGTTTGAATGTCC	GGACATTCAAACTGCTCCG
2645	GGAGCAGTTTGAATGTCCA	TGGACATTCAAACTGCTCC
2646	GAGCAGTTTGAATGTCCAC	GTGGACATTCAAACTGCTC
2647	AGCAGTTTGAATGTCCACG	CGTGGACATTCAAACTGCT
2648	GCAGTTTGAATGTCCACGC	GCGTGGACATTCAAACTGC
2649	CAGTTTGAATGTCCACGCG	CGCGTGGACATTCAAACTG
2650	AGTTTGAATGTCCACGCGG	CCGCGTGGACATTCAAACT
2651	GTTTGAATGTCCACGCGGC	GCCGCGTGGACATTCAAAC
2652	TTTGAATGTCCACGCGGCT	AGCCGCGTGGACATTCAAA
2653	TTGAATGTCCACGCGGCTG	CAGCCGCGTGGACATTCAA
2654	TGAATGTCCACGCGGCTGC	GCAGCCGCGTGGACATTCA
2655	GAATGTCCACGCGGCTGCC	GGCAGCCGCGTGGACATTC
2656	AATGTCCACGCGGCTGCCC	GGGCAGCCGCGTGGACATT
2657	ATGTCCACGCGGCTGCCCT	AGGGCAGCCGCGTGGACAT
2658	TGTCCACGCGGCTGCCCTG	CAGGGCAGCCGCGTGGACA
2659	GTCCACGCGGCTGCCCTGA	TCAGGGCAGCCGCGTGGAC
2660	TCCACGCGGCTGCCCTGAG	CTCAGGGCAGCCGCGTGGA
2661	CCACGCGGCTGCCCTGAGG	CCTCAGGGCAGCCGCGTGG
2662	CACGCGGCTGCCCTGAGGT	ACCTCAGGGCAGCCGCGTG
2663	ACGCGGCTGCCCTGAGGTC	GACCTCAGGGCAGCCGCGT
2664	CGCGGCTGCCCTGAGGTCG	CGACCTCAGGGCAGCCGCG
2665	GCGGCTGCCCTGAGGTCGA	TCGACCTCAGGGCAGCCGC
2666	CGGCTGCCCTGAGGTCGAG	CTCGACCTCAGGGCAGCCG
2667	GGCTGCCCTGAGGTCGAGG	CCTCGACCTCAGGGCAGCC
2668	GCTGCCCTGAGGTCGAGGA	TCCTCGACCTCAGGGCAGC
2669	CTGCCCTGAGGTCGAGGAG	CTCCTCGACCTCAGGGCAG
2670	TGCCCTGAGGTCGAGGAGA	TCTCCTCGACCTCAGGGCA
2671	GCCCTGAGGTCGAGGAGAG	CTCTCCTCGACCTCAGGGC
2672	CCCTGAGGTCGAGGAGAGG	CCTCTCCTCGACCTCAGGG
2673	CCTGAGGTCGAGGAGAGGC	GCCTCTCCTCGACCTCAGG
2674	CTGAGGTCGAGGAGAGGCC	GGCCTCTCCTCGACCTCAG
2675	TGAGGTCGAGGAGAGGCCG	CGGCCTCTCCTCGACCTCA
2676	GAGGTCGAGGAGAGGCCGG	CCGGCCTCTCCTCGACCTC
2677	AGGTCGAGGAGAGGCCGGT	ACCGGCCTCTCCTCGACCT
2678	GGTCGAGGAGAGGCCGGTT	AACCGGCCTCTCCTCGACC
2679	GTCGAGGAGAGGCCGGTTG	CAACCGGCCTCTCCTCGAC
2680	TCGAGGAGAGGCCGGTTGC	GCAACCGGCCTCTCCTCGA
2681	CGAGGAGAGGCCGGTTGCT	AGCAACCGGCCTCTCCTCG
2682	GAGGAGAGGCCGGTTGCTC	GAGCAACCGGCCTCTCCTC
2683	AGGAGAGGCCGGTTGCTCG	CGAGCAACCGGCCTCTCCT
2684	GGAGAGGCCGGTTGCTCGG	CCGAGCAACCGGCCTCTCC
2685	GAGAGGCCGGTTGCTCGGC	GCCGAGCAACCGGCCTCTC
2686	AGAGGCCGGTTGCTCGGCT	AGCCGAGCAACCGGCCTCT
2687	GAGGCCGGTTGCTCGGCTC	GAGCCGAGCAACCGGCCTC
2688	AGGCCGGTTGCTCGGCTCC	GGAGCCGAGCAACCGGCCT
2689	GGCCGGTTGCTCGGCTCCG	CGGAGCCGAGCAACCGGCC
2690	GCCGGTTGCTCGGCTCCGG	CCGGAGCCGAGCAACCGGC
2691	CCGGTTGCTCGGCTCCGGG	CCCGGAGCCGAGCAACCGG
2692	CGGTTGCTCGGCTCCGGGC	GCCCGGAGCCGAGCAACCG
2693	GGTTGCTCGGCTCCGGGCC	GGCCCGGAGCCGAGCAACC
2694	GTTGCTCGGCTCCGGGCCC	GGGCCCGGAGCCGAGCAAC
2695	TTGCTCGGCTCCGGGCCCT	AGGGCCCGGAGCCGAGCAA
2696	TGCTCGGCTCCGGGCCCTC	GAGGGCCCGGAGCCGAGCA
2697	GCTCGGCTCCGGGCCCTCA	TGAGGGCCCGGAGCCGAGC
2698	CTCGGCTCCGGGCCCTCAA	TTGAGGGCCCGGAGCCGAG
2699	TCGGCTCCGGGCCCTCAAA	TTTGAGGGCCCGGAGCCGA
2700	CGGCTCCGGGCCCTCAAAA	TTTTGAGGGCCCGGAGCCG
2701	GGCTCCGGGCCCTCAAAAG	CTTTTGAGGGCCCGGAGCC
2702	GCTCCGGGCCCTCAAAAGG	CCTTTTGAGGGCCCGGAGC
2703	CTCCGGGCCCTCAAAAGGG	CCCTTTTGAGGGCCCGGAG
2704	TCCGGGCCCTCAAAAGGGC	GCCCTTTTGAGGGCCCGGA
2705	CCGGGCCCTCAAAAGGGCA	TGCCCTTTTGAGGGCCCGG
2706	CGGGCCCTCAAAAGGGCAG	CTGCCCTTTTGAGGGCCCG
2707	GGGCCCTCAAAAGGGCAGG	CCTGCCCTTTTGAGGGCCC
2708	GGCCCTCAAAAGGGCAGGC	GCCTGCCCTTTTGAGGGCC
2709	GCCCTCAAAAGGGCAGGCA	TGCCTGCCCTTTTGAGGGC
2710	CCCTCAAAAGGGCAGGCAG	CTGCCTGCCCTTTTGAGGG
2711	CCTCAAAAGGGCAGGCAGC	GCTGCCTGCCCTTTTGAGG
2712	CTCAAAAGGGCAGGCAGCC	GGCTGCCTGCCCTTTTGAG
2713	TCAAAAGGGCAGGCAGCCC	GGGCTGCCTGCCCTTTTGA
2714	CAAAAGGGCAGGCAGCCCC	GGGGCTGCCTGCCCTTTTG
2715	AAAAGGGCAGGCAGCCCCG	CGGGGCTGCCTGCCCTTTT
2716	AAAGGGCAGGCAGCCCCGA	TCGGGGCTGCCTGCCCTTT
2717	AAGGGCAGGCAGCCCCGAG	CTCGGGGCTGCCTGCCCTT
2718	AGGGCAGGCAGCCCCGAGG	CCTCGGGGCTGCCTGCCCT
2719	GGGCAGGCAGCCCCGAGGT	ACCTCGGGGCTGCCTGCCC
2720	GGCAGGCAGCCCCGAGGTC	GACCTCGGGGCTGCCTGCC
2721	GCAGGCAGCCCCGAGGTCC	GGACCTCGGGGCTGCCTGC
2722	CAGGCAGCCCCGAGGTCCA	TGGACCTCGGGGCTGCCTG
2723	AGGCAGCCCCGAGGTCCAG	CTGGACCTCGGGGCTGCCT
2724	GGCAGCCCCGAGGTCCAGG	CCTGGACCTCGGGGCTGCC
2725	GCAGCCCCGAGGTCCAGGG	CCCTGGACCTCGGGGCTGC
2726	CAGCCCCGAGGTCCAGGGA	TCCCTGGACCTCGGGGCTG
2727	AGCCCCGAGGTCCAGGGAG	CTCCCTGGACCTCGGGGCT
2728	GCCCCGAGGTCCAGGGAGC	GCTCCCTGGACCTCGGGGC
2729	CCCCGAGGTCCAGGGAGCA	TGCTCCCTGGACCTCGGGG
2730	CCCGAGGTCCAGGGAGCAA	TTGCTCCCTGGACCTCGGG
2731	CCGAGGTCCAGGGAGCAAT	ATTGCTCCCTGGACCTCGG
2732	CGAGGTCCAGGGAGCAATG	CATTGCTCCCTGGACCTCG
2733	GAGGTCCAGGGAGCAATGG	CCATTGCTCCCTGGACCTC
2734	AGGTCCAGGGAGCAATGGG	CCCATTGCTCCCTGGACCT
2735	GGTCCAGGGAGCAATGGGC	GCCCATTGCTCCCTGGACC
2736	GTCCAGGGAGCAATGGGCA	TGCCCATTGCTCCCTGGAC
2737	TCCAGGGAGCAATGGGCAG	CTGCCCATTGCTCCCTGGA
2738	CCAGGGAGCAATGGGCAGT	ACTGCCCATTGCTCCCTGG
2739	CAGGGAGCAATGGGCAGTC	GACTGCCCATTGCTCCCTG
2740	AGGGAGCAATGGGCAGTCC	GGACTGCCCATTGCTCCCT
2741	GGGAGCAATGGGCAGTCCA	TGGACTGCCCATTGCTCCC
2742	GGAGCAATGGGCAGTCCAG	CTGGACTGCCCATTGCTCC
2743	GAGCAATGGGCAGTCCAGC	GCTGGACTGCCCATTGCTC
2744	AGCAATGGGCAGTCCAGCC	GGCTGGACTGCCCATTGCT
2745	GCAATGGGCAGTCCAGCCC	GGGCTGGACTGCCCATTGC
2746	CAATGGGCAGTCCAGCCCC	GGGGCTGGACTGCCCATTG
2747	AATGGGCAGTCCAGCCCCC	GGGGGCTGGACTGCCCATT
2748	ATGGGCAGTCCAGCCCCCA	TGGGGGCTGGACTGCCCAT
2749	TGGGCAGTCCAGCCCCCAA	TTGGGGGCTGGACTGCCCA
2750	GGGCAGTCCAGCCCCCAAG	CTTGGGGGCTGGACTGCCC
2751	GGCAGTCCAGCCCCCAAGC	GCTTGGGGGCTGGACTGCC
2752	GCAGTCCAGCCCCCAAGCG	CGCTTGGGGGCTGGACTGC
2753	CAGTCCAGCCCCCAAGCGG	CCGCTTGGGGGCTGGACTG
2754	AGTCCAGCCCCCAAGCGGC	GCCGCTTGGGGGCTGGACT
2755	GTCCAGCCCCCAAGCGGCC	GGCCGCTTGGGGGCTGGAC
2756	TCCAGCCCCCAAGCGGCCA	TGGCCGCTTGGGGGCTGGA
2757	CCAGCCCCCAAGCGGCCAC	GTGGCCGCTTGGGGGCTGG
2758	CAGCCCCCAAGCGGCCACC	GGTGGCCGCTTGGGGGCTG
2759	AGCCCCCAAGCGGCCACCG	CGGTGGCCGCTTGGGGGCT
2760	GCCCCCAAGCGGCCACCGG	CCGGTGGCCGCTTGGGGGC
2761	CCCCCAAGCGGCCACCGGA	TCCGGTGGCCGCTTGGGGG
2762	CCCCAAGCGGCCACCGGAC	GTCCGGTGGCCGCTTGGGG
2763	CCCAAGCGGCCACCGGACC	GGTCCGGTGGCCGCTTGGG
2764	CCAAGCGGCCACCGGACCC	GGGTCCGGTGGCCGCTTGG
2765	CAAGCGGCCACCGGACCCT	AGGGTCCGGTGGCCGCTTG
2766	AAGCGGCCACCGGACCCTT	AAGGGTCCGGTGGCCGCTT
2767	AGCGGCCACCGGACCCTTT	AAAGGGTCCGGTGGCCGCT
2768	GCGGCCACCGGACCCTTTT	AAAAGGGTCCGGTGGCCGC
2769	CGGCCACCGGACCCTTTTC	GAAAAGGGTCCGGTGGCCG
2770	GGCCACCGGACCCTTTTCC	GGAAAAGGGTCCGGTGGCC
2771	GCCACCGGACCCTTTTCCA	TGGAAAAGGGTCCGGTGGC
2772	CCACCGGACCCTTTTCCAG	CTGGAAAAGGGTCCGGTGG
2773	CACCGGACCCTTTTCCAGG	CCTGGAAAAGGGTCCGGTG
2774	ACCGGACCCTTTTCCAGGC	GCCTGGAAAAGGGTCCGGT
2775	CCGGACCCTTTTCCAGGCA	TGCCTGGAAAAGGGTCCGG
2776	CGGACCCTTTTCCAGGCAC	GTGCCTGGAAAAGGGTCCG
2777	GGACCCTTTTCCAGGCACT	AGTGCCTGGAAAAGGGTCC
2778	GACCCTTTTCCAGGCACTG	CAGTGCCTGGAAAAGGGTC
2779	ACCCTTTTCCAGGCACTGC	GCAGTGCCTGGAAAAGGGT
2780	CCCTTTTCCAGGCACTGCA	TGCAGTGCCTGGAAAAGGG
2781	CCTTTTCCAGGCACTGCAG	CTGCAGTGCCTGGAAAAGG
2782	CTTTTCCAGGCACTGCAGA	TCTGCAGTGCCTGGAAAAG
2783	TTTTCCAGGCACTGCAGAA	TTCTGCAGTGCCTGGAAAA
2784	TTTCCAGGCACTGCAGAAC	GTTCTGCAGTGCCTGGAAA
2785	TTCCAGGCACTGCAGAACA	TGTTCTGCAGTGCCTGGAA
2786	TCCAGGCACTGCAGAACAG	CTGTTCTGCAGTGCCTGGA
2787	CCAGGCACTGCAGAACAGG	CCTGTTCTGCAGTGCCTGG
2788	CAGGCACTGCAGAACAGGG	CCCTGTTCTGCAGTGCCTG
2789	AGGCACTGCAGAACAGGGG	CCCCTGTTCTGCAGTGCCT
2790	GGCACTGCAGAACAGGGGG	CCCCCTGTTCTGCAGTGCC
2791	GCACTGCAGAACAGGGGGC	GCCCCCTGTTCTGCAGTGC
2792	CACTGCAGAACAGGGGGCT	AGCCCCCTGTTCTGCAGTG
2793	ACTGCAGAACAGGGGGCTG	CAGCCCCCTGTTCTGCAGT
2794	CTGCAGAACAGGGGGCTGG	CCAGCCCCCTGTTCTGCAG
2795	TGCAGAACAGGGGGCTGGG	CCCAGCCCCCTGTTCTGCA
2796	GCAGAACAGGGGGCTGGGG	CCCCAGCCCCCTGTTCTGC
2797	CAGAACAGGGGGCTGGGGG	CCCCCAGCCCCCTGTTCTG
2798	AGAACAGGGGGCTGGGGGT	ACCCCCAGCCCCCTGTTCT
2799	GAACAGGGGGCTGGGGGTT	AACCCCCAGCCCCCTGTTC
2800	AACAGGGGGCTGGGGGTTG	CAACCCCCAGCCCCCTGTT
2801	ACAGGGGGCTGGGGGTTGG	CCAACCCCCAGCCCCCTGT
2802	CAGGGGGCTGGGGGTTGGC	GCCAACCCCCAGCCCCCTG
2803	AGGGGGCTGGGGGTTGGCA	TGCCAACCCCCAGCCCCCT
2804	GGGGGCTGGGGGTTGGCAG	CTGCCAACCCCCAGCCCCC
2805	GGGGCTGGGGGTTGGCAGG	CCTGCCAACCCCCAGCCCC
2806	GGGCTGGGGGTTGGCAGGA	TCCTGCCAACCCCCAGCCC
2807	GGCTGGGGGTTGGCAGGAG	CTCCTGCCAACCCCCAGCC
2808	GCTGGGGGTTGGCAGGAGG	CCTCCTGCCAACCCCCAGC
2809	CTGGGGGTTGGCAGGAGGT	ACCTCCTGCCAACCCCCAG
2810	TGGGGGTTGGCAGGAGGTG	CACCTCCTGCCAACCCCCA
2811	GGGGGTTGGCAGGAGGTGC	GCACCTCCTGCCAACCCCC
2812	GGGGTTGGCAGGAGGTGCG	CGCACCTCCTGCCAACCCC
2813	GGGTTGGCAGGAGGTGCGG	CCGCACCTCCTGCCAACCC
2814	GGTTGGCAGGAGGTGCGGG	CCCGCACCTCCTGCCAACC
2815	GTTGGCAGGAGGTGCGGGA	TCCCGCACCTCCTGCCAAC
2816	TTGGCAGGAGGTGCGGGAC	GTCCCGCACCTCCTGCCAA
2817	TGGCAGGAGGTGCGGGACA	TGTCCCGCACCTCCTGCCA
2818	GGCAGGAGGTGCGGGACAC	GTGTCCCGCACCTCCTGCC
2819	GCAGGAGGTGCGGGACACA	TGTGTCCCGCACCTCCTGC
2820	CAGGAGGTGCGGGACACAT	ATGTGTCCCGCACCTCCTG
2821	AGGAGGTGCGGGACACATC	GATGTGTCCCGCACCTCCT
2822	GGAGGTGCGGGACACATCG	CGATGTGTCCCGCACCTCC
2823	GAGGTGCGGGACACATCGA	TCGATGTGTCCCGCACCTC
2824	AGGTGCGGGACACATCGAT	ATCGATGTGTCCCGCACCT
2825	GGTGCGGGACACATCGATA	TATCGATGTGTCCCGCACC
2826	GTGCGGGACACATCGATAG	CTATCGATGTGTCCCGCAC
2827	TGCGGGACACATCGATAGG	CCTATCGATGTGTCCCGCA
2828	GCGGGACACATCGATAGGG	CCCTATCGATGTGTCCCGC
2829	CGGGACACATCGATAGGGA	TCCCTATCGATGTGTCCCG
2830	GGGACACATCGATAGGGAA	TTCCCTATCGATGTGTCCC
2831	GGACACATCGATAGGGAAC	GTTCCCTATCGATGTGTCC
2832	GACACATCGATAGGGAACA	TGTTCCCTATCGATGTGTC
2833	ACACATCGATAGGGAACAA	TTGTTCCCTATCGATGTGT
2834	CACATCGATAGGGAACAAG	CTTGTTCCCTATCGATGTG
2835	ACATCGATAGGGAACAAGG	CCTTGTTCCCTATCGATGT
2836	CATCGATAGGGAACAAGGA	TCCTTGTTCCCTATCGATG
2837	ATCGATAGGGAACAAGGAT	ATCCTTGTTCCCTATCGAT
2838	TCGATAGGGAACAAGGATG	CATCCTTGTTCCCTATCGA
2839	CGATAGGGAACAAGGATGT	ACATCCTTGTTCCCTATCG
2840	GATAGGGAACAAGGATGTG	CACATCCTTGTTCCCTATC
2841	ATAGGGAACAAGGATGTGG	CCACATCCTTGTTCCCTAT
2842	TAGGGAACAAGGATGTGGA	TCCACATCCTTGTTCCCTA
2843	AGGGAACAAGGATGTGGAC	GTCCACATCCTTGTTCCCT
2844	GGGAACAAGGATGTGGACT	AGTCCACATCCTTGTTCCC
2845	GGAACAAGGATGTGGACTC	GAGTCCACATCCTTGTTCC
2846	GAACAAGGATGTGGACTCG	CGAGTCCACATCCTTGTTC
2847	AACAAGGATGTGGACTCGG	CCGAGTCCACATCCTTGTT
2848	ACAAGGATGTGGACTCGGG	CCCGAGTCCACATCCTTGT
2849	CAAGGATGTGGACTCGGGA	TCCCGAGTCCACATCCTTG
2850	AAGGATGTGGACTCGGGAC	GTCCCGAGTCCACATCCTT
2851	AGGATGTGGACTCGGGACA	TGTCCCGAGTCCACATCCT
2852	GGATGTGGACTCGGGACAG	CTGTCCCGAGTCCACATCC
2853	GATGTGGACTCGGGACAGC	GCTGTCCCGAGTCCACATC
2854	ATGTGGACTCGGGACAGCA	TGCTGTCCCGAGTCCACAT
2855	TGTGGACTCGGGACAGCAT	ATGCTGTCCCGAGTCCACA
2856	GTGGACTCGGGACAGCATG	CATGCTGTCCCGAGTCCAC
2857	TGGACTCGGGACAGCATGA	TCATGCTGTCCCGAGTCCA
2858	GGACTCGGGACAGCATGAT	ATCATGCTGTCCCGAGTCC
2859	GACTCGGGACAGCATGATG	CATCATGCTGTCCCGAGTC
2860	ACTCGGGACAGCATGATGA	TCATCATGCTGTCCCGAGT
2861	CTCGGGACAGCATGATGAG	CTCATCATGCTGTCCCGAG
2862	TCGGGACAGCATGATGAGC	GCTCATCATGCTGTCCCGA
2863	CGGGACAGCATGATGAGCA	TGCTCATCATGCTGTCCCG
2864	GGGACAGCATGATGAGCAG	CTGCTCATCATGCTGTCCC
2865	GGACAGCATGATGAGCAGA	TCTGCTCATCATGCTGTCC
2866	GACAGCATGATGAGCAGAA	TTCTGCTCATCATGCTGTC
2867	ACAGCATGATGAGCAGAAA	TTTCTGCTCATCATGCTGT
2868	CAGCATGATGAGCAGAAAG	CTTTCTGCTCATCATGCTG
2869	AGCATGATGAGCAGAAAGG	CCTTTCTGCTCATCATGCT
2870	GCATGATGAGCAGAAAGGA	TCCTTTCTGCTCATCATGC
2871	CATGATGAGCAGAAAGGAC	GTCCTTTCTGCTCATCATG
2872	ATGATGAGCAGAAAGGACC	GGTCCTTTCTGCTCATCAT
2873	TGATGAGCAGAAAGGACCC	GGGTCCTTTCTGCTCATCA
2874	GATGAGCAGAAAGGACCCC	GGGGTCCTTTCTGCTCATC
2875	ATGAGCAGAAAGGACCCCA	TGGGGTCCTTTCTGCTCAT
2876	TGAGCAGAAAGGACCCCAA	TTGGGGTCCTTTCTGCTCA
2877	GAGCAGAAAGGACCCCAAG	CTTGGGGTCCTTTCTGCTC
2878	AGCAGAAAGGACCCCAAGA	TCTTGGGGTCCTTTCTGCT
2879	GCAGAAAGGACCCCAAGAT	ATCTTGGGGTCCTTTCTGC
2880	CAGAAAGGACCCCAAGATG	CATCTTGGGGTCCTTTCTG
2881	AGAAAGGACCCCAAGATGG	CCATCTTGGGGTCCTTTCT
2882	GAAAGGACCCCAAGATGGC	GCCATCTTGGGGTCCTTTC
2883	AAAGGACCCCAAGATGGCC	GGCCATCTTGGGGTCCTTT
2884	AAGGACCCCAAGATGGCCA	TGGCCATCTTGGGGTCCTT
2885	AGGACCCCAAGATGGCCAG	CTGGCCATCTTGGGGTCCT
2886	GGACCCCAAGATGGCCAGG	CCTGGCCATCTTGGGGTCC
2887	GACCCCAAGATGGCCAGGC	GCCTGGCCATCTTGGGGTC
2888	ACCCCAAGATGGCCAGGCC	GGCCTGGCCATCTTGGGGT
2889	CCCCAAGATGGCCAGGCCA	TGGCCTGGCCATCTTGGGG
2890	CCCAAGATGGCCAGGCCAG	CTGGCCTGGCCATCTTGGG
2891	CCAAGATGGCCAGGCCAGT	ACTGGCCTGGCCATCTTGG
2892	CAAGATGGCCAGGCCAGTC	GACTGGCCTGGCCATCTTG
2893	AAGATGGCCAGGCCAGTCT	AGACTGGCCTGGCCATCTT
2894	AGATGGCCAGGCCAGTCTC	GAGACTGGCCTGGCCATCT
2895	GATGGCCAGGCCAGTCTCC	GGAGACTGGCCTGGCCATC
2896	ATGGCCAGGCCAGTCTCCA	TGGAGACTGGCCTGGCCAT
2897	TGGCCAGGCCAGTCTCCAG	CTGGAGACTGGCCTGGCCA
2898	GGCCAGGCCAGTCTCCAGG	CCTGGAGACTGGCCTGGCC
2899	GCCAGGCCAGTCTCCAGGA	TCCTGGAGACTGGCCTGGC
2900	CCAGGCCAGTCTCCAGGAC	GTCCTGGAGACTGGCCTGG
2901	CAGGCCAGTCTCCAGGACC	GGTCCTGGAGACTGGCCTG
2902	AGGCCAGTCTCCAGGACCC	GGGTCCTGGAGACTGGCCT
2903	GGCCAGTCTCCAGGACCCG	CGGGTCCTGGAGACTGGCC
2904	GCCAGTCTCCAGGACCCGG	CCGGGTCCTGGAGACTGGC
2905	CCAGTCTCCAGGACCCGGG	CCCGGGTCCTGGAGACTGG
2906	CAGTCTCCAGGACCCGGGA	TCCCGGGTCCTGGAGACTG
2907	AGTCTCCAGGACCCGGGAC	GTCCCGGGTCCTGGAGACT
2908	GTCTCCAGGACCCGGGACT	AGTCCCGGGTCCTGGAGAC
2909	TCTCCAGGACCCGGGACTT	AAGTCCCGGGTCCTGGAGA
2910	CTCCAGGACCCGGGACTTC	GAAGTCCCGGGTCCTGGAG
2911	TCCAGGACCCGGGACTTCA	TGAAGTCCCGGGTCCTGGA
2912	CCAGGACCCGGGACTTCAG	CTGAAGTCCCGGGTCCTGG
2913	CAGGACCCGGGACTTCAGG	CCTGAAGTCCCGGGTCCTG
2914	AGGACCCGGGACTTCAGGA	TCCTGAAGTCCCGGGTCCT
2915	GGACCCGGGACTTCAGGAC	GTCCTGAAGTCCCGGGTCC
2916	GACCCGGGACTTCAGGACA	TGTCCTGAAGTCCCGGGTC
2917	ACCCGGGACTTCAGGACAT	ATGTCCTGAAGTCCCGGGT
2918	CCCGGGACTTCAGGACATA	TATGTCCTGAAGTCCCGGG
2919	CCGGGACTTCAGGACATAC	GTATGTCCTGAAGTCCCGG
2920	CGGGACTTCAGGACATACC	GGTATGTCCTGAAGTCCCG
2921	GGGACTTCAGGACATACCA	TGGTATGTCCTGAAGTCCC
2922	GGACTTCAGGACATACCAT	ATGGTATGTCCTGAAGTCC
2923	GACTTCAGGACATACCATG	CATGGTATGTCCTGAAGTC
2924	ACTTCAGGACATACCATGC	GCATGGTATGTCCTGAAGT
2925	CTTCAGGACATACCATGCC	GGCATGGTATGTCCTGAAG
2926	TTCAGGACATACCATGCCT	AGGCATGGTATGTCCTGAA
2927	TCAGGACATACCATGCCTG	CAGGCATGGTATGTCCTGA
2928	CAGGACATACCATGCCTGG	CCAGGCATGGTATGTCCTG
2929	AGGACATACCATGCCTGGC	GCCAGGCATGGTATGTCCT
2930	GGACATACCATGCCTGGCT	AGCCAGGCATGGTATGTCC
2931	GACATACCATGCCTGGCTC	GAGCCAGGCATGGTATGTC
2932	ACATACCATGCCTGGCTCT	AGAGCCAGGCATGGTATGT
2933	CATACCATGCCTGGCTCTC	GAGAGCCAGGCATGGTATG
2934	ATACCATGCCTGGCTCTCC	GGAGAGCCAGGCATGGTAT
2935	TACCATGCCTGGCTCTCCC	GGGAGAGCCAGGCATGGTA
2936	ACCATGCCTGGCTCTCCCT	AGGGAGAGCCAGGCATGGT
2937	CCATGCCTGGCTCTCCCTG	CAGGGAGAGCCAGGCATGG
2938	CATGCCTGGCTCTCCCTGC	GCAGGGAGAGCCAGGCATG
2939	ATGCCTGGCTCTCCCTGCA	TGCAGGGAGAGCCAGGCAT
2940	TGCCTGGCTCTCCCTGCAA	TTGCAGGGAGAGCCAGGCA
2941	GCCTGGCTCTCCCTGCAAA	TTTGCAGGGAGAGCCAGGC
2942	CCTGGCTCTCCCTGCAAAA	TTTTGCAGGGAGAGCCAGG
2943	CTGGCTCTCCCTGCAAAAC	GTTTTGCAGGGAGAGCCAG
2944	TGGCTCTCCCTGCAAAACT	AGTTTTGCAGGGAGAGCCA
2945	GGCTCTCCCTGCAAAACTG	CAGTTTTGCAGGGAGAGCC
2946	GCTCTCCCTGCAAAACTGG	CCAGTTTTGCAGGGAGAGC
2947	CTCTCCCTGCAAAACTGGC	GCCAGTTTTGCAGGGAGAG
2948	TCTCCCTGCAAAACTGGCT	AGCCAGTTTTGCAGGGAGA
2949	CTCCCTGCAAAACTGGCTC	GAGCCAGTTTTGCAGGGAG
2950	TCCCTGCAAAACTGGCTCA	TGAGCCAGTTTTGCAGGGA
2951	CCCTGCAAAACTGGCTCAA	TTGAGCCAGTTTTGCAGGG
2952	CCTGCAAAACTGGCTCAAT	ATTGAGCCAGTTTTGCAGG
2953	CTGCAAAACTGGCTCAATG	CATTGAGCCAGTTTTGCAG
2954	TGCAAAACTGGCTCAATGC	GCATTGAGCCAGTTTTGCA
2955	GCAAAACTGGCTCAATGCC	GGCATTGAGCCAGTTTTGC
2956	CAAAACTGGCTCAATGCCA	TGGCATTGAGCCAGTTTTG
2957	AAAACTGGCTCAATGCCAA	TTGGCATTGAGCCAGTTTT
2958	AAACTGGCTCAATGCCAAA	TTTGGCATTGAGCCAGTTT
2959	AACTGGCTCAATGCCAAAG	CTTTGGCATTGAGCCAGTT
2960	ACTGGCTCAATGCCAAAGT	ACTTTGGCATTGAGCCAGT
2961	CTGGCTCAATGCCAAAGTT	AACTTTGGCATTGAGCCAG
2962	TGGCTCAATGCCAAAGTTG	CAACTTTGGCATTGAGCCA
2963	GGCTCAATGCCAAAGTTGT	ACAACTTTGGCATTGAGCC
2964	GCTCAATGCCAAAGTTGTG	CACAACTTTGGCATTGAGC
2965	CTCAATGCCAAAGTTGTGC	GCACAACTTTGGCATTGAG
2966	TCAATGCCAAAGTTGTGCC	GGCACAACTTTGGCATTGA
2967	CAATGCCAAAGTTGTGCCC	GGGCACAACTTTGGCATTG
2968	AATGCCAAAGTTGTGCCCA	TGGGCACAACTTTGGCATT
2969	ATGCCAAAGTTGTGCCCAG	CTGGGCACAACTTTGGCAT
2970	TGCCAAAGTTGTGCCCAGG	CCTGGGCACAACTTTGGCA
2971	GCCAAAGTTGTGCCCAGGC	GCCTGGGCACAACTTTGGC
2972	CCAAAGTTGTGCCCAGGCA	TGCCTGGGCACAACTTTGG
2973	CAAAGTTGTGCCCAGGCAG	CTGCCTGGGCACAACTTTG
2974	AAAGTTGTGCCCAGGCAGC	GCTGCCTGGGCACAACTTT
2975	AAGTTGTGCCCAGGCAGCT	AGCTGCCTGGGCACAACTT
2976	AGTTGTGCCCAGGCAGCTG	CAGCTGCCTGGGCACAACT
2977	GTTGTGCCCAGGCAGCTGG	CCAGCTGCCTGGGCACAAC
2978	TTGTGCCCAGGCAGCTGGA	TCCAGCTGCCTGGGCACAA
2979	TGTGCCCAGGCAGCTGGAG	CTCCAGCTGCCTGGGCACA
2980	GTGCCCAGGCAGCTGGAGA	TCTCCAGCTGCCTGGGCAC
2981	TGCCCAGGCAGCTGGAGAG	CTCTCCAGCTGCCTGGGCA
2982	GCCCAGGCAGCTGGAGAGG	CCTCTCCAGCTGCCTGGGC
2983	CCCAGGCAGCTGGAGAGGG	CCCTCTCCAGCTGCCTGGG
2984	CCAGGCAGCTGGAGAGGGA	TCCCTCTCCAGCTGCCTGG
2985	CAGGCAGCTGGAGAGGGAG	CTCCCTCTCCAGCTGCCTG
2986	AGGCAGCTGGAGAGGGAGG	CCTCCCTCTCCAGCTGCCT
2987	GGCAGCTGGAGAGGGAGGA	TCCTCCCTCTCCAGCTGCC
2988	GCAGCTGGAGAGGGAGGAG	CTCCTCCCTCTCCAGCTGC
2989	CAGCTGGAGAGGGAGGAGG	CCTCCTCCCTCTCCAGCTG
2990	AGCTGGAGAGGGAGGAGGG	CCCTCCTCCCTCTCCAGCT
2991	GCTGGAGAGGGAGGAGGGC	GCCCTCCTCCCTCTCCAGC
2992	CTGGAGAGGGAGGAGGGCA	TGCCCTCCTCCCTCTCCAG
2993	TGGAGAGGGAGGAGGGCAC	GTGCCCTCCTCCCTCTCCA
2994	GGAGAGGGAGGAGGGCACG	CGTGCCCTCCTCCCTCTCC
2995	GAGAGGGAGGAGGGCACGC	GCGTGCCCTCCTCCCTCTC
2996	AGAGGGAGGAGGGCACGCC	GGCGTGCCCTCCTCCCTCT
2997	GAGGGAGGAGGGCACGCCT	AGGCGTGCCCTCCTCCCTC
2998	AGGGAGGAGGGCACGCCTG	CAGGCGTGCCCTCCTCCCT
2999	GGGAGGAGGGCACGCCTGC	GCAGGCGTGCCCTCCTCCC
3000	GGAGGAGGGCACGCCTGCC	GGCAGGCGTGCCCTCCTCC
3001	GAGGAGGGCACGCCTGCCA	TGGCAGGCGTGCCCTCCTC
3002	AGGAGGGCACGCCTGCCAC	GTGGCAGGCGTGCCCTCCT
3003	GGAGGGCACGCCTGCCACT	AGTGGCAGGCGTGCCCTCC
3004	GAGGGCACGCCTGCCACTC	GAGTGGCAGGCGTGCCCTC
3005	AGGGCACGCCTGCCACTCT	AGAGTGGCAGGCGTGCCCT
3006	GGGCACGCCTGCCACTCTC	GAGAGTGGCAGGCGTGCCC
3007	GGCACGCCTGCCACTCTCA	TGAGAGTGGCAGGCGTGCC
3008	GCACGCCTGCCACTCTCAG	CTGAGAGTGGCAGGCGTGC
3009	CACGCCTGCCACTCTCAGC	GCTGAGAGTGGCAGGCGTG
3010	ACGCCTGCCACTCTCAGCA	TGCTGAGAGTGGCAGGCGT
3011	CGCCTGCCACTCTCAGCAA	TTGCTGAGAGTGGCAGGCG
3012	GCCTGCCACTCTCAGCAAG	CTTGCTGAGAGTGGCAGGC
3013	CCTGCCACTCTCAGCAAGT	ACTTGCTGAGAGTGGCAGG
3014	CTGCCACTCTCAGCAAGTG	CACTTGCTGAGAGTGGCAG
3015	TGCCACTCTCAGCAAGTGC	GCACTTGCTGAGAGTGGCA
3016	GCCACTCTCAGCAAGTGCG	CGCACTTGCTGAGAGTGGC
3017	CCACTCTCAGCAAGTGCGG	CCGCACTTGCTGAGAGTGG
3018	CACTCTCAGCAAGTGCGGA	TCCGCACTTGCTGAGAGTG
3019	ACTCTCAGCAAGTGCGGAG	CTCCGCACTTGCTGAGAGT
3020	CTCTCAGCAAGTGCGGAGA	TCTCCGCACTTGCTGAGAG
3021	TCTCAGCAAGTGCGGAGAT	ATCTCCGCACTTGCTGAGA
3022	CTCAGCAAGTGCGGAGATC	GATCTCCGCACTTGCTGAG
3023	TCAGCAAGTGCGGAGATCG	CGATCTCCGCACTTGCTGA
3024	CAGCAAGTGCGGAGATCGC	GCGATCTCCGCACTTGCTG
3025	AGCAAGTGCGGAGATCGCC	GGCGATCTCCGCACTTGCT
3026	GCAAGTGCGGAGATCGCCT	AGGCGATCTCCGCACTTGC
3027	CAAGTGCGGAGATCGCCTC	GAGGCGATCTCCGCACTTG
3028	AAGTGCGGAGATCGCCTCT	AGAGGCGATCTCCGCACTT
3029	AGTGCGGAGATCGCCTCTG	CAGAGGCGATCTCCGCACT
3030	GTGCGGAGATCGCCTCTGG	CCAGAGGCGATCTCCGCAC
3031	TGCGGAGATCGCCTCTGGG	CCCAGAGGCGATCTCCGCA
3032	GCGGAGATCGCCTCTGGGA	TCCCAGAGGCGATCTCCGC
3033	CGGAGATCGCCTCTGGGAG	CTCCCAGAGGCGATCTCCG
3034	GGAGATCGCCTCTGGGAGG	CCTCCCAGAGGCGATCTCC
3035	GAGATCGCCTCTGGGAGGG	CCCTCCCAGAGGCGATCTC
3036	AGATCGCCTCTGGGAGGGG	CCCCTCCCAGAGGCGATCT
3037	GATCGCCTCTGGGAGGGGA	TCCCCTCCCAGAGGCGATC
3038	ATCGCCTCTGGGAGGGGAG	CTCCCCTCCCAGAGGCGAT
3039	TCGCCTCTGGGAGGGGAGC	GCTCCCCTCCCAGAGGCGA
3040	CGCCTCTGGGAGGGGAGCT	AGCTCCCCTCCCAGAGGCG
3041	GCCTCTGGGAGGGGAGCTG	CAGCTCCCCTCCCAGAGGC
3042	CCTCTGGGAGGGGAGCTGC	GCAGCTCCCCTCCCAGAGG
3043	CTCTGGGAGGGGAGCTGCA	TGCAGCTCCCCTCCCAGAG
3044	TCTGGGAGGGGAGCTGCAG	CTGCAGCTCCCCTCCCAGA
3045	CTGGGAGGGGAGCTGCAGC	GCTGCAGCTCCCCTCCCAG
3046	TGGGAGGGGAGCTGCAGCA	TGCTGCAGCTCCCCTCCCA
3047	GGGAGGGGAGCTGCAGCAG	CTGCTGCAGCTCCCCTCCC
3048	GGAGGGGAGCTGCAGCAGG	CCTGCTGCAGCTCCCCTCC
3049	GAGGGGAGCTGCAGCAGGA	TCCTGCTGCAGCTCCCCTC
3050	AGGGGAGCTGCAGCAGGAG	CTCCTGCTGCAGCTCCCCT
3051	GGGGAGCTGCAGCAGGAGG	CCTCCTGCTGCAGCTCCCC
3052	GGGAGCTGCAGCAGGAGGA	TCCTCCTGCTGCAGCTCCC
3053	GGAGCTGCAGCAGGAGGAA	TTCCTCCTGCTGCAGCTCC
3054	GAGCTGCAGCAGGAGGAAG	CTTCCTCCTGCTGCAGCTC
3055	AGCTGCAGCAGGAGGAAGA	TCTTCCTCCTGCTGCAGCT
3056	GCTGCAGCAGGAGGAAGAC	GTCTTCCTCCTGCTGCAGC
3057	CTGCAGCAGGAGGAAGACA	TGTCTTCCTCCTGCTGCAG
3058	TGCAGCAGGAGGAAGACAC	GTGTCTTCCTCCTGCTGCA
3059	GCAGCAGGAGGAAGACACA	TGTGTCTTCCTCCTGCTGC
3060	CAGCAGGAGGAAGACACAG	CTGTGTCTTCCTCCTGCTG
3061	AGCAGGAGGAAGACACAGC	GCTGTGTCTTCCTCCTGCT
3062	GCAGGAGGAAGACACAGCC	GGCTGTGTCTTCCTCCTGC
3063	CAGGAGGAAGACACAGCCA	TGGCTGTGTCTTCCTCCTG
3064	AGGAGGAAGACACAGCCAC	GTGGCTGTGTCTTCCTCCT
3065	GGAGGAAGACACAGCCACC	GGTGGCTGTGTCTTCCTCC
3066	GAGGAAGAGACAGCCACCA	TGGTGGCTGTGTCTTCCTC
3067	AGGAAGACACAGCCACCAA	TTGGTGGCTGTGTCTTCCT
3068	GGAAGACACAGCCACCAAC	GTTGGTGGCTGTGTCTTCC
3069	GAAGACACAGCCACCAACT	AGTTGGTGGCTGTGTCTTC
3070	AAGACACAGCCACCAACTC	GAGTTGGTGGCTGTGTCTT
3071	AGACACAGCCACCAACTCC	GGAGTTGGTGGCTGTGTCT
3072	GACACAGCCACCAACTCCA	TGGAGTTGGTGGCTGTGTC
3073	ACACAGCCACCAACTCCAG	CTGGAGTTGGTGGCTGTGT
3074	CACAGCCACCAACTCCAGC	GCTGGAGTTGGTGGCTGTG
3075	ACAGCCACCAACTCCAGCT	AGCTGGAGTTGGTGGCTGT
3076	CAGCCACCAACTCCAGCTC	GAGCTGGAGTTGGTGGCTG
3077	AGCCACCAACTCCAGCTCT	AGAGCTGGAGTTGGTGGCT
3078	GCCACCAACTCCAGCTCTG	CAGAGCTGGAGTTGGTGGC
3079	CCACCAACTCCAGCTCTGA	TCAGAGCTGGAGTTGGTGG
3080	CACCAACTCCAGCTCTGAG	CTCAGAGCTGGAGTTGGTG
3081	ACCAACTCCAGCTCTGAGG	CCTCAGAGCTGGAGTTGGT
3082	CCAACTCCAGCTCTGAGGA	TCCTCAGAGCTGGAGTTGG
3083	CAACTCCAGCTCTGAGGAA	TTCCTCAGAGCTGGAGTTG
3084	AACTCCAGCTCTGAGGAAG	CTTCCTCAGAGCTGGAGTT
3085	ACTCCAGCTCTGAGGAAGG	CCTTCCTCAGAGCTGGAGT
3086	CTCCAGCTCTGAGGAAGGC	GCCTTCCTCAGAGCTGGAG
3087	TCCAGCTCTGAGGAAGGCC	GGCCTTCCTCAGAGCTGGA
3088	CCAGCTCTGAGGAAGGCCC	GGGCCTTCCTCAGAGCTGG
3089	CAGCTCTGAGGAAGGCCCA	TGGGCCTTCCTCAGAGCTG
3090	AGCTCTGAGGAAGGCCCAG	CTGGGCCTTCCTCAGAGCT
3091	GCTCTGAGGAAGGCCCAGG	CCTGGGCCTTCCTCAGAGC
3092	CTCTGAGGAAGGCCCAGGG	CCCTGGGCCTTCCTCAGAG
3093	TCTGAGGAAGGCCCAGGGT	ACCCTGGGCCTTCCTCAGA
3094	CTGAGGAAGGCCCAGGGTC	GACCCTGGGCCTTCCTCAG
3095	TGAGGAAGGCCCAGGGTCC	GGACCCTGGGCCTTCCTCA
3096	GAGGAAGGCCCAGGGTCCG	CCGACCCTGGGCCTTCCTC
3097	AGGAAGGCCCAGGGTCCGG	CCGGACCCTGGGCCTTCCT
3098	GGAAGGCCCAGGGTCCGGC	GCCGGACCCTGGGCCTTCC
3099	GAAGGCCCAGGGTCCGGCC	GGCCGGACCCTGGGCCTTC
3100	AAGGCCCAGGGTCCGGCCC	GGGCCGGACCCTGGGCCTT
3101	AGGCCCAGGGTCCGGCCCT	AGGGCCGGACCCTGGGCCT
3102	GGCCCAGGGTCCGGCCCTG	CAGGGCCGGACCCTGGGCC
3103	GCCCAGGGTCCGGCCCTGA	TCAGGGCCGGACCCTGGGC
3104	CCCAGGGTCCGGCCCTGAC	GTCAGGGCCGGACCCTGGG
3105	CCAGGGTCCGGCCCTGACA	TGTCAGGGCCGGACCCTGG
3106	CAGGGTCCGGCCCTGACAG	CTGTCAGGGCCGGACCCTG
3107	AGGGTCCGGCCCTGACAGC	GCTGTCAGGGCCGGACCCT
3108	GGGTCCGGCCCTGACAGCG	GGCTGTCAGGGCCGGACCC
3109	GGTCCGGCCCTGACAGCCG	CGGCTGTCAGGGCCGGACC
3110	GTCCGGCCCTGACAGCCGG	CCGGCTGTCAGGGCCGGAC
3111	TCCGGCCCTGACAGCCGGC	GCCGGCTGTCAGGGCCGGA
3112	CCGGCCCTGACAGCCGGCT	AGCCGGCTGTCAGGGCCGG
3113	CGGCCCTGACAGCCGGCTC	GAGCCGGCTGTCAGGGCCG
3114	GGCCCTGACAGCCGGCTCA	TGAGCCGGCTGTCAGGGCC
3115	GCCCTGACAGCCGGCTCAG	CTGAGCCGGCTGTCAGGGC
3116	CCCTGACAGCCGGCTCAGC	GCTGAGCCGGCTGTCAGGG
3117	CCTGACAGCCGGCTCAGCA	TGCTGAGCCGGCTGTCAGG
3118	CTGACAGCCGGCTCAGCAC	GTGCTGAGCCGGCTGTCAG
3119	TGACAGCCGGCTCAGCACA	TGTGCTGAGCCGGCTGTCA
3120	GACAGCCGGCTCAGCACAG	CTGTGCTGAGCCGGCTGTC
3121	ACAGCCGGCTCAGCACAGG	CCTGTGCTGAGCCGGCTGT
3122	CAGCCGGCTCAGCACAGGC	GCCTGTGCTGAGCCGGCTG
3123	AGCCGGCTCAGCACAGGCC	GGCCTGTGCTGAGCCGGCT
3124	GCCGGCTCAGCACAGGCCT	AGGCCTGTGCTGAGCCGGC
3125	CCGGCTCAGCACAGGCCTC	GAGGCCTGTGCTGAGCCGG
3126	CGGCTCAGCACAGGCCTCG	CGAGGCCTGTGCTGAGCCG
3127	GGCTCAGCACAGGCCTCGC	GCGAGGCCTGTGCTGAGCC
3128	GCTCAGCACAGGCCTCGCC	GGCGAGGCCTGTGCTGAGC
3129	CTCAGCACAGGCCTCGCCA	TGGCGAGGCCTGTGCTGAG
3130	TCAGCACAGGCCTCGCCAA	TTGGCGAGGCCTGTGCTGA
3131	CAGCACAGGCCTCGCCAAG	CTTGGCGAGGCCTGTGCTG
3132	AGCACAGGCCTCGCCAAGC	GCTTGGCGAGGCCTGTGCT
3133	GCACAGGCCTCGCCAAGCA	TGCTTGGCGAGGCCTGTGC
3134	CACAGGCCTCGCCAAGCAC	GTGCTTGGCGAGGCCTGTG
3135	ACAGGCCTCGCCAAGCACC	GGTGCTTGGCGAGGCCTGT
3136	CAGGCCTCGCCAAGCACCT	AGGTGCTTGGCGAGGCCTG
3137	AGGCCTCGCCAAGCACCTG	CAGGTGCTTGGCGAGGCCT
3138	GGCCTCGCCAAGCACCTGC	GCAGGTGCTTGGCGAGGCC
3139	GCCTCGCCAAGCACCTGCT	AGCAGGTGCTTGGCGAGGC
3140	CCTCGCCAAGCACCTGCTC	GAGCAGGTGCTTGGCGAGG
3141	CTCGCCAAGCACCTGCTCA	TGAGCAGGTGCTTGGCGAG
3142	TCGCCAAGCACCTGCTCAG	CTGAGCAGGTGCTTGGCGA
3143	CGCCAAGCACCTGCTCAGT	ACTGAGCAGGTGCTTGGCG
3144	GCCAAGCACCTGCTCAGTG	CACTGAGCAGGTGCTTGGC
3145	CCAAGCACCTGCTCAGTGG	CCACTGAGCAGGTGCTTGG
3146	CAAGCACCTGCTCAGTGGT	ACCACTGAGCAGGTGCTTG
3147	AAGCACCTGCTCAGTGGTT	AACCACTGAGCAGGTCCTT
3148	AGCACCTGCTCAGTGGTTT	AAACCACTGAGCAGGTGCT
3149	GCACCTGCTCAGTGGTTTG	CAAACCACTGAGCAGGTGC
3150	CACCTGCTCAGTGGTTTGG	CCAAACCACTGAGCAGGTG
3151	ACCTGCTCAGTGGTTTGGG	CCCAAACCACTGAGCAGGT
3152	CCTGCTCAGTGGTTTGGGG	CCCCAAACCACTGAGCAGG
3153	CTGCTCAGTGGTTTGGGGG	CCCCCAAACCACTGAGCAG
3154	TGCTCAGTGGTTTGGGGGA	TCCCCCAAACCACTGAGCA
3155	GCTCAGTGGTTTGGGGGAC	GTCCCCCAAACCACTGAGC
3156	CTCAGTGGTTTGGGGGACC	GGTCCCCCAAACCACTGAG
3157	TCAGTGGTTTGGGGGACCG	CGGTCCCCCAAACCACTGA
3158	CAGTGGTTTGGGGGACCGA	TCGGTCCCCCAAACCACTG
3159	AGTGGTTTGGGGGACCGAC	GTCGGTCCCCCAAACCACT
3160	GTGGTTTGGGGGACCGACT	AGTCGGTCCCCCAAACCAC
3161	TGGTTTGGGGGACCGACTG	CAGTCGGTCCCCCAAACCA
3162	GGTTTGGGGGACCGACTGT	ACAGTCGGTCCCCCAAACC
3163	GTTTGGGGGACCGACTGTG	CACAGTCGGTCCCCCAAAC
3164	TTTGGGGGACCGACTGTGC	GCACAGTCGGTCCCCCAAA
3165	TTGGGGGACCGACTGTGCC	GGCACAGTCGGTCCCCCAA
3166	TGGGGGACCGACTGTGCCG	CGGCACAGTCGGTCCCCCA
3167	GGGGGACCGACTGTGCCGC	GCGGCACAGTCGGTCCCCC
3168	GGGGACCGACTGTGCCGCC	GGCGGCACAGTCGGTCCCC
3169	GGGACCGACTGTGCCGCCT	AGGCGGCACAGTCGGTCCC
3170	GGACCGACTGTGCCGCCTG	CAGGCGGCACAGTCGGTCC
3171	GACCGACTGTGCCGCCTGC	GCAGGCGGCACAGTCGGTC
3172	ACCGACTGTGCCGCCTGCT	AGCAGGCGGCACAGTCGGT
3173	CCGACTGTGCCGCCTGCTG	CAGCAGGCGGCACAGTCGG
3174	CGACTGTGCCGCCTGCTGC	GCAGCAGGCGGCACAGTCG
3175	GACTGTGCCGCCTGCTGCG	CGCAGCAGGCGGCACAGTC
3176	ACTGTGCCGCCTGCTGCGG	CCGCAGCAGGCGGCACAGT
3177	CTGTGCCGCCTGCTGCGGA	TCCGCAGCAGGCGGCACAG
3178	TGTGCCGCCTGCTGCGGAG	CTCCGCAGCAGGCGGCACA
3179	GTGCCGCCTGCTGCGGAGG	CCTCCGCAGCAGGCGGCAC
3180	TGCCGCCTGCTGCGGAGGG	CCCTCCGCAGCAGGCGGCA
3181	GCCGCCTGCTGCGGAGGGA	TCCCTCCGCAGCAGGCGGC
3182	CCGCCTGCTGCGGAGGGAG	CTCCCTCCGCAGCAGGCGG
3183	CGCCTGCTGCGGAGGGAGC	GCTCCCTCCGCAGCAGGCG
3184	GCCTGCTGCGGAGGGAGCG	CGCTCCCTCCGCAGCAGGC
3185	CCTGCTGCGGAGGGAGCGG	CCGCTCCCTCCGCAGCAGG
3186	CTGCTGCGGAGGGAGCGGG	CCCGCTCCGTCCGCAGCAG
3187	TGCTGCGGAGGGAGCGGGA	TCCCGCTCCCTCCGCAGCA
3188	GCTGCGGAGGGAGCGGGAG	CTCCCGCTCCCTCCGCAGC
3189	CTGCGGAGGGAGCGGGAGG	CCTCCCGCTCCCTCCGCAG
3190	TGCGGAGGGAGCGGGAGGC	GCCTCCCGCTCCCTCCGCA
3191	GCGGAGGGAGCGGGAGGCC	GGCCTCCCGCTCCCTCCGC
3192	CGGAGGGAGCGGGAGGCCC	GGGCCTCCCGCTCCCTCCG
3193	GGAGGGAGCGGGAGGCCCT	AGGGCCTCCCGCTCCCTCC
3194	GAGGGAGCGGGAGGCCCTG	CAGGGCCTCCCGCTCCCTC
3195	AGGGAGCGGGAGGCCCTGG	CCAGGGCCTCCCGCTCCCT
3196	GGGAGCGGGAGGCCCTGGC	GCCAGGGCCTCCCGCTCCC
3197	GGAGCGGGAGGCCCTGGCT	AGCCAGGGCCTCCCGCTCC
3198	GAGCGGGAGGCCCTGGCTT	AAGCCAGGGCCTCCCGCTC
3199	AGCGGGAGGCCCTGGCTTG	CAAGCCAGGGCCTCCCGCT
3200	GCGGGAGGCCCTGGCTTGG	CCAAGCCAGGGCCTCCCGC
3201	CGGGAGGCCCTGGCTTGGG	CCCAAGCCAGGGCCTCCCG
3202	GGGAGGCCCTGGCTTGGGC	GCCCAAGCCAGGGCCTCCC
3203	GGAGGCCCTGGCTTGGGCC	GGCCCAAGCCAGGGCCTCC
3204	GAGGCCCTGGCTTGGGCCC	GGGCCCAAGCCAGGGCCTC
3205	AGGCCCTGGCTTGGGCCCA	TGGGCCCAAGCCAGGGCCT
3206	GGCCCTGGCTTGGGCCCAG	CTGGGCCCAAGCCAGGGCC
3207	GCCCTGGCTTGGGCCCAGC	GCTGGGCCCAAGCCAGGGC
3208	CCCTGGCTTGGGCCCAGCG	CGCTGGGCCCAAGCCAGGG
3209	CCTGGCTTGGGCCCAGCGG	CCGCTGGGCCCAAGCCAGG
3210	CTGGCTTGGGCCCAGCGGG	CCCGCTGGGCCCAAGCCAG
3211	TGGCTTGGGCCCAGCGGGA	TCCCGCTGGGCCCAAGCCA
3212	GGCTTGGGCCCAGCGGGAA	TTCCCGCTGGGCCCAAGCC
3213	GCTTGGGCCCAGCGGGAAG	CTTCCCGCTGGGCCCAAGC
3214	CTTGGGCCCAGCGGGAAGG	CCTTCCCGCTGGGCCCAAG
3215	TTGGGCCCAGCGGGAAGGC	GCCTTCCCGCTGGGCCCAA
3216	TGGGCCCAGCGGGAAGGCC	GGCCTTCCCGCTGGGCCCA
3217	GGGCCCAGCGGGAAGGCCA	TGGCCTTCCCGCTGGGCCC
3218	GGCCCAGCGGGAAGGCCAA	TTGGCCTTCCCGCTGGGCC
3219	GCCCAGCGGGAAGGCCAAG	CTTGGCCTTCCCGCTGGGC
3220	CCCAGCGGGAAGGCCAAGG	CCTTGGCCTTCCCGCTGGG
3221	CCAGCGGGAAGGCCAAGGG	CCCTTGGCCTTCCCGCTGG
3222	CAGCGGGAAGGCCAAGGGC	GCCCTTGGCCTTCCCGCTG
3223	AGCGGGAAGGCCAAGGGCC	GGCCCTTGGCCTTCCCGCT
3224	GCGGGAAGGCCAAGGGCCA	TGGCCCTTGGCCTTCCCGC
3225	CGGGAAGGCCAAGGGCCAG	CTGGCCCTTGGCCTTCCCG
3226	GGGAAGGCCAAGGGCCAGC	GCTGGCCCTTGGCCTTCCC
3227	GGAAGGCCAAGGGCCAGCC	GGCTGGCCCTTGGCCTTCC
3228	GAAGGCCAAGGGCCAGCCG	CGGCTGGCCCTTGGCCTTC
3229	AAGGCCAAGGGCCAGCCGT	ACGGCTGGCCCTTGGCCTT
3230	AGGCCAAGGGCCAGCCGTG	CACGGCTGGCCCTTGGCCT
3231	GGCCAAGGGCCAGCCGTGA	TCACGGCTGGCCCTTGGCC
3232	GCCAAGGGCCAGCCGTGAC	GTCACGGCTGGCCCTTGGC
3233	CCAAGGGCCAGCCGTGACA	TGTCACGGCTGGCCCTTGG
3234	CAAGGGCCAGCCGTGACAG	CTGTCACGGCTGGCCCTTG
3235	AAGGGCCAGCCGTGACAGA	TCTGTCACGGCTGGCCCTT
3236	AGGGCCAGCCGTGACAGAG	CTCTGTCACGGCTGGCCCT
3237	GGGCCAGCCGTGACAGAGG	CCTCTGTCACGGCTGGCCC
3238	GGCCAGCCGTGACAGAGGA	TCCTCTGTCACGGCTGGCC
3239	GCCAGCCGTGACAGAGGAC	GTCCTCTGTCACGGCTGGC
3240	CCAGCCGTGACAGAGGACA	TGTCCTCTGTCACGGCTGG
3241	CAGCCGTGACAGAGGACAG	CTGTCCTCTGTCACGGCTG
3242	AGCCGTGACAGAGGACAGC	GCTGTCCTCTGTCACGGCT
3243	GCCGTGACAGAGGACAGCC	GGCTGTCCTCTGTCACGGC
3244	CCGTGACACAGGACAGCCC	GGGCTGTCCTCTGTCACGG
3245	CGTGACAGAGGACAGCCCA	TGGGCTGTCCTCTGTCACG
3246	GTGACAGAGGACAGCCCAG	CTGGGCTGTCCTCTGTCAC
3247	TGACAGAGGACAGCCCAGG	CCTGGGCTGTCCTCTGTCA
3248	GACAGAGGACAGCCCAGGC	GCCTGGGCTGTCCTCTGTC
3249	ACAGAGGACAGCCCAGGCA	TGCCTGGGCTGTCCTCTGT
3250	CAGAGGACAGCCCAGGCAT	ATGCCTGGGCTGTCCTCTG
3251	AGAGGACAGCCCAGGCATT	AATGCCTGGGCTGTCCTCT
3252	GAGGACAGCCCAGGCATTC	GAATGCCTGGGCTGTCCTC
3253	AGGACAGCCCAGGCATTCC	GGAATGCCTGGGCTGTCCT
3254	GGACAGCCCAGGCATTCCA	TGGAATGCCTGGGCTGTCC
3255	GACAGCCCAGGCATTCCAC	GTGGAATGCCTGGGCTGTC
3256	ACAGCCCAGGCATTCCACG	CGTGGAATGCCTGGGCTGT
3257	CAGCCCAGGCATTCCACGC	GCGTGGAATGCCTGGGCTG
3258	AGCCCAGGCATTCCACGCT	AGCGTGGAATGCCTGGGCT
3259	GCCCAGGCATTCCACGCTG	CAGCGTGGAATGCCTGGGC
3260	CCCAGGCATTCCACGCTGC	GCAGCGTGGAATGCCTGGG
3261	CCAGGCATTCCACGCTGCT	AGCAGCGTGGAATGCCTGG
3262	CAGGCATTCCACGCTGCTG	CAGCAGCGTGGAATGCCTG
3263	AGGCATTCCACGCTGCTGC	GCAGCAGCGTGGAATGCCT
3264	GGCATTCCACGCTGCTGCA	TGCAGCAGCGTGGAATGCC
3265	GCATTCCACGCTGCTGCAG	CTGCAGCAGCGTGGAATGC
3266	CATTCCACGCTGCTGCAGC	GCTGCAGCAGCGTGGAATG
3267	ATTCCACGCTGCTGCAGCC	GGCTGCAGCAGCGTGGAAT
3268	TTCCACGCTGCTGCAGCCG	CGGCTGCAGCAGCGTGGAA
3269	TCCACGCTGCTGCAGCCGT	ACGGCTGCAGCAGCGTGGA
3270	CCACGCTGCTGCAGCCGTT	AACGGCTGCAGCAGCGTGG
3271	CACGCTGCTGCAGCCGTTG	CAACGGCTGCAGCAGCGTG
3272	ACGCTGCTGCAGCCGTTGC	GCAACGGCTGCAGCAGCGT
3273	CGCTGCTGCAGCCGTTGCC	GGCAACGGCTGCAGCAGCG
3274	GCTGCTGCAGCCGTTGCCA	TGGCAACGGCTGCAGCAGC
3275	CTGCTGCAGCCGTTGCCAC	GTGGCAACGGCTGCAGCAG
3276	TGCTGCAGCCGTTGCCACC	GGTGGCAACGGCTGCAGCA
3277	GCTGCAGCCGTTGCCACCA	TGGTGGCAACGGCTGCAGC
3278	CTGCAGCCGTTGCCACCAT	ATGGTGGCAACGGCTGCAG
3279	TGCAGCCGTTGCCACCATG	CATGGTGGCAACGGCTGCA
3280	GCAGCCGTTGCCACCATGG	CCATGGTGGCAACGGCTGC
3281	CAGCCGTTGCCACCATGGA	TCCATGGTGGCAACGGCTG
3282	AGCCGTTGCCACCATGGAC	GTCCATGGTGGCAACGGCT
3283	GCCGTTGCCACCATGGACT	AGTCCATGGTGGCAAGGGC
3284	CCGTTGCCACCATGGACTC	GAGTCCATGGTGGCAACGG
3285	CGTTGCCACCATGGACTCT	AGAGTCCATGGTGGCAACG
3286	GTTGCCACCATGGACTCTT	AAGAGTCCATGGTGGCAAC
3287	TTGCCACCATGGACTCTTC	GAAGAGTCCATGGTGGCAA
3288	TGCCACCATGGACTCTTCA	TGAAGAGTCCATGGTGGCA
3289	GCCACCATGGACTCTTCAA	TTGAAGAGTCCATGGTGGC
3290	CCACCATGGACTCTTCAAC	GTTGAAGAGTCCATGGTGG
3291	CACCATGGACTCTTCAACA	TGTTGAAGAGTCCATGGTG
3292	ACCATGGACTCTTCAACAC	GTGTTGAAGAGTCCATGGT
3293	CCATGGACTCTTCAACACC	GGTGTTGAAGAGTCCATGG
3294	CATGGACTCTTCAACACCC	GGGTGTTGAAGAGTCCATG
3295	ATGGACTCTTCAACACCCA	TGGGTGTTGAAGAGTCCAT
3296	TGGACTCTTCAACACCCAC	GTGGGTGTTGAAGAGTCCA
3297	GGACTCTTCAACACCCACT	AGTGGGTGTTGAAGAGTCC
3298	GACTCTTCAACACCCACTG	CAGTGGGTGTTGAAGAGTC
3299	ACTCTTCAACACCCACTGG	CCAGTGGGTGTTGAAGAGT
3300	CTCTTCAACACCCACTGGC	GCCAGTGGGTGTTGAAGAG
3301	TCTTCAACACCCACTGGCG	CGCCAGTGGGTGTTGAAGA
3302	CTTCAACACCCACTGGCGA	TCGCCAGTGGGTGTTGAAG
3303	TTCAACACCCACTGGCGAT	ATCGCCAGTGGGTGTTGAA
3304	TCAACACCCACTGGCGATG	CATCGCCAGTGGGTGTTGA
3305	CAACACCCACTGGCGATGT	ACATCGCCAGTGGGTGTTG
3306	AACACCCACTGGCGATGTC	GACATCGCCAGTGGGTGTT
3307	ACACCCACTGGCGATGTCC	GGACATCGCCAGTGGGTGT
3308	CACCCACTGGCGATGTCCC	GGGACATCGCCAGTGGGTG
3309	ACCCACTGGCGATGTCCCC	GGGGACATCGCCAGTGGGT
3310	CCCACTGGCGATGTCCCCG	CGGGGACATCGCCAGTGGG
3311	CCACTGGCGATGTCCCCGC	GCGGGGACATCGCCAGTGG
3312	CACTGGCGATGTCCCCGCT	AGCGGGGACATCGCCAGTG
3313	ACTGGCGATGTCCCCGCTG	CAGCGGGGACATCGCCAGT
3314	CTGGCGATGTCCCCGCTGC	GCAGCGGGGACATCGCCAG
3315	TGGCGATGTCCCCGCTGCA	TGCAGCGGGGACATCGCCA
3316	GGCGATGTCCCCGCTGCAG	CTGCAGCGGGGACATCGCC
3317	GCGATGTCCCCGCTGCAGC	GCTGCAGCGGGGACATCGC
3318	CGATGTCCCCGCTGCAGCC	GGCTGCAGCGGGGACATCG
3319	GATGTCCCCGCTGCAGCCA	TGGCTGCAGCGGGGACATC
3320	ATGTCCCCGCTGCAGCCAC	GTGGCTGCAGCGGGGACAT
3321	TGTCCCCGCTGCAGCCACC	GGTGGCTGCAGCGGGGACA
3322	GTCCCCGCTGCAGCCACCG	CGGTGGCTGCAGCGGGGAC
3323	TCCCCGCTGCAGCCACCGG	CCGGTGGCTGCAGCGGGGA
3324	CCCCGCTGCAGCCACCGGC	GCCGGTGGCTGCAGCGGGG
3325	CCCGCTGCAGCCACCGGCT	AGCCGGTGGCTGCAGCGGG
3326	CCGCTGCAGCCACCGGCTG	CAGCCGGTGGCTGCAGCGG
3327	CGCTGCAGCCACCGGCTGT	ACAGCCGGTGGCTGCAGCG
3328	GCTGCAGCCACCGGCTGTG	CACAGCCGGTGGCTGCAGC
3329	CTGCAGCCACCGGCTGTGT	ACACAGCCGGTGGCTGCAG
3330	TGCAGCCACCGGCTGTGTG	CACACAGCCGGTGGCTGCA
3331	GCAGCCACCGGCTGTGTGT	ACACACAGCCGGTGGCTGC
3332	CAGCCACCGGCTGTGTGTG	CACACACAGCCGGTGGCTG
3333	AGCCACCGGCTGTGTGTGG	CCACACACAGCCGGTGGCT
3334	GCCACCGGCTGTGTGTGGC	GCCACACACAGCCGGTGGC
3335	CCACCGGCTGTGTGTGGCC	GGCCACACACAGCCGGTGG
3336	CACCGGCTGTGTGTGGCCT	AGGCCACACACAGCCGGTG
3337	ACCGGCTGTGTGTGGCCTG	CAGGCCACACACAGCCGGT
3338	CCGGCTGTGTGTGGCCTGT	ACAGGCCACACACAGCCGG
3339	CGGCTGTGTGTGGCCTGTG	CACAGGCCACACACAGCCG
3340	GGCTGTGTGTGGCCTGTGG	CCACAGGCCACACACAGCC
3341	GCTGTGTGTGGCCTGTGGT	ACCACAGGCCACACACAGC
3342	CTGTGTGTGGCCTGTGGTC	GACCACAGGCCACACACAG
3343	TGTGTGTGGCCTGTGGTCG	CGACCACAGGCCACACACA
3344	GTGTGTGGCCTGTGGTCGT	ACGACCACAGGCCACACAC
3345	TGTGTGGCCTGTGGTCGTG	CACGACCACAGGCCACACA
3346	GTGTGGCCTGTGGTCGTGT	ACACGACCACAGGCCACAC
3347	TGTGGCCTGTGGTCGTGTG	CACACGACCACAGGCCACA
3348	GTGGCCTGTGGTCGTGTGG	CCACACGACCACAGGCCAC
3349	TGGCCTGTGGTCGTGTGGC	GCCACACGACCACAGGCCA
3350	GGCCTGTGGTCGTGTGGCA	TGCCACACGACCACAGGCC
3351	GCCTGTGGTCGTGTGGCAG	CTGCCACACGACCACAGGC
3352	CCTGTGGTCGTGTGGCAGG	CCTGCCACACGACCACAGG
3353	CTGTGGTCGTGTGGCAGGC	GCCTGCCACACGACCACAG
3354	TGTGGTCGTGTGGCAGGCA	TGCCTGCCACACGACCACA
3355	GTGGTCGTGTGGCAGGCAC	GTGCCTGCCACACGACCAC
3356	TGGTCGTGTGGCAGGCACT	AGTGCCTGCCACACGACCA
3357	GGTCGTGTGGCAGGCACTG	CAGTGCCTGCCACACGACC
3358	GTCGTGTGGCAGGCACTGG	CCAGTGCCTGCCACACGAC
3359	TCGTGTGGCAGGCACTGGG	CCCAGTGCCTGCCACACGA
3360	CGTGTGGCAGGCACTGGGC	GCCCAGTGCCTGCCACACG
3361	GTGTGGCAGGCACTGGGCG	CGCCCAGTGCCTGCCACAC
3362	TGTGGCAGGCACTGGGCGG	CCGCCCAGTGCCTGCCACA
3363	GTGGCAGGCACTGGGCGGG	CCCGCCCAGTGCCTGCCAC
3364	TGGCAGGCACTGGGCGGGC	GCCCGCCCAGTGCCTGCCA
3365	GGCAGGCACTGGGCGGGCC	GGCCCGCCCAGTGCCTGCC
3366	GCAGGCACTGGGCGGGCCA	TGGCCCGCCCAGTGCCTGC
3367	CAGGCACTGGGCGGGCCAG	CTGGCCCGCCCAGTGCCTG
3368	AGGCACTGGGCGGGCCAGG	CCTGGCCCGCCCAGTGCCT
3369	GGCACTGGGCGGGCCAGGG	CCCTGGCCCGCCCAGTGCC
3370	GCACTGGGCGGGCCAGGGA	TCCCTGGCCCGCCCAGTGC
3371	CACTGGGCGGGCCAGGGAG	CTCCCTGGCCCGCCCAGTG
3372	ACTGGGCGGGCCAGGGAGA	TCTCCCTGGCCCGCCCAGT
3373	CTGGGCGGGCCAGGGAGAA	TTCTCCCTGGCCCGCCCAG
3374	TGGGCGGGCCAGGGAGAAA	TTTCTCCCTGGCCCGCCCA
3375	GGGCGGGCCAGGGAGAAAG	CTTTCTCCCTGGCCCGCCC
3376	GGCGGGCCAGGGAGAAAGC	GCTTTCTCCCTGGCCCGCC
3377	GCGGGCCAGGGAGAAAGCA	TGCTTTCTCCCTGGCCCGC
3378	CGGGCCAGGGAGAAAGCAG	CTGCTTTCTCCCTGGCCCG
3379	GGGCCAGGGAGAAAGCAGG	CCTGCTTTCTCCCTGGCCC
3380	GGCCAGGGAGAAAGCAGGC	GCCTGCTTTCTCCCTGGCC
3381	GCCAGGGAGAAAGCAGGCT	AGCCTGCTTTCTCCCTGGC
3382	CCAGGGAGAAAGCAGGCTT	AAGCCTGCTTTCTCCCTGG
3383	CAGGGAGAAAGCAGGCTTT	AAAGCCTGCTTTCTCCCTG
3384	AGGGAGAAAGCAGGCTTTC	GAAAGCCTGCTTTCTCCCT
3385	GGGAGAAAGCAGGCTTTCA	TGAAAGCCTGCTTTCTCCC
3386	GGAGAAAGCAGGCTTTCAG	CTGAAAGCCTGCTTTCTCC
3387	GAGAAAGCAGGCTTTCAGG	CCTGAAAGCCTGCTTTCTC
3388	AGAAAGCAGGCTTTCAGGA	TCCTGAAAGCCTGCTTTCT
3389	GAAAGCAGGCTTTCAGGAG	CTCCTGAAAGCCTGCTTTC
3390	AAAGCAGGCTTTCAGGAGC	GCTCCTGAAAGCCTGCTTT
3391	AAGCAGGCTTTCAGGAGCA	TGCTCCTGAAAGCCTGCTT
3392	AGCAGGCTTTCAGGAGCAG	CTGCTCCTGAAAGCCTGCT
3393	GCAGGCTTTCAGGAGCAGT	ACTGCTCCTGAAAGCCTGC
3394	CAGGCTTTCAGGAGCAGTC	GACTGCTCCTGAAAGCCTG
3395	AGGCTTTCAGGAGCAGTCC	GGACTGCTCCTGAAAGCCT
3396	GGCTTTCAGGAGCAGTCCG	CGGACTGCTCCTGAAAGCC
3397	GCTTTCAGGAGCAGTCCGC	GCGGACTGCTCCTGAAAGC
3398	CTTTCAGGAGCAGTCCGCG	CGCGGACTGCTCCTGAAAG
3399	TTTCAGGAGCAGTCCGCGG	CCGCGGACTGCTCCTGAAA
3400	TTCAGGAGCAGTCCGCGGA	TCCGCGGACTGCTCCTGAA
3401	TCAGGAGCAGTCCGCGGAG	CTCCGCGGACTGCTCCTGA
3402	CAGGAGCAGTCCGCGGAGG	CCTCCGCGGACTGCTCCTG
3403	AGGAGCAGTCCGCGGAGGA	TCCTCCGCGGACTGCTCCT
3404	GGAGCAGTCCGCGGAGGAG	CTCCTCCGCGGACTGCTCC
3405	GAGCAGTCCGCGGAGGAGT	ACTCCTCCGCGGACTGCTC
3406	AGCAGTCCGCGGAGGAGTG	CACTCCTCCGCGGACTGCT
3407	GCAGTCCGCGGAGGAGTGC	GCACTCCTCCGCGGACTGC
3408	CAGTCCGCGGAGGAGTGCA	TGCACTCCTCCGCGGACTG
3409	AGTCCGCGGAGGAGTGCAC	GTGCACTCCTCCGCGGACT
3410	GTCCGCGGAGGAGTGCACG	CGTGCACTCCTCCGCGGAC
3411	TCCGCGGAGGAGTGCACGC	GCGTGCACTCCTCCGCGGA
3412	CCGCGGAGGAGTGCACGCA	TGCGTGCACTCCTCCGCGG
3413	CGCGGAGGAGTGCACGCAG	CTGCGTGCACTCCTCCGCG
3414	GCGGAGGAGTGCACGCAGG	CCTGCGTGCACTCCTCCGC
3415	CGGAGGAGTGCACGCAGGA	TCCTGCGTGCACTCCTCCG
3416	GGAGGAGTGCACGCAGGAG	CTCCTGCGTGCACTCCTCC
3417	GAGGAGTGCACGCAGGAGG	CCTCCTGCGTGCACTCCTC
3418	AGGAGTGCACGCAGGAGGC	GCCTCCTGCGTGCACTCCT
3419	GGAGTGCACGCAGGAGGCC	GGCCTCCTGCGTGCACTCC
3420	GAGTGCACGCAGGAGGCCG	CGGCCTCCTGCGTGCACTC
3421	AGTGCACGCAGGAGGCCGG	CCGGCCTCCTGCGTGCACT
3422	GTGCACGCAGGAGGCCGGG	CCCGGCCTCCTGCGTGCAC
3423	TGCACGCAGGAGGCCGGGC	GCCCGGCCTCCTGCGTGCA
3424	GCACGCAGGAGGCCGGGCA	TGCCCGGCCTCCTGCGTGC
3425	CACGCAGGAGGCCGGGCAC	GTGCCCGGCCTCCTGCGTG
3426	ACGCAGGAGGCCGGGCACG	CGTGCCCGGCCTCCTGCGT
3427	CGCAGGAGGCCGGGCACGC	GCGTGCCCGGCCTCCTGCG
3428	GCAGGAGGCCGGGCACGCT	AGCGTGCCCGGCCTCCTGC
3429	CAGGAGGCCGGGCACGCTG	CAGCGTGCCCGGCCTCCTG
3430	AGGAGGCCGGGCACGCTGC	GCAGCGTGCCCGGCCTCCT
3431	GGAGGCCGGGCACGCTGCC	GGCAGCGTGCCCGGCCTCC
3432	GAGGCCGGGCACGCTGCCT	AGGCAGCGTGCCCGGCCTC
3433	AGGCCGGGCACGCTGCCTG	CAGGCAGCGTGCCCGGCCT
3434	GGCCGGGCACGCTGCCTGT	ACAGGCAGCGTGCCCGGCC
3435	GCCGGGCACGCTGCCTGTT	AACAGGCAGCGTGCCCGGC
3436	CCGGGCACGCTGCCTGTTC	GAACAGGCAGCGTGCCCGG
3437	CGGGCACGCTGCCTGTTCC	GGAACAGGCAGCGTGCCCG
3438	GGGCACGCTGCCTGTTCCC	GGGAACAGGCAGCGTGCCC
3439	GGCACGCTGCCTGTTCCCT	AGGGAACAGGCAGCGTGCC
3440	GCACGCTGCCTGTTCCCTG	CAGGGAACAGGCAGCGTGC
3441	CACGCTGCCTGTTCCCTGA	TCAGGGAACAGGCAGCGTG
3442	ACGCTGCCTGTTCCCTGAT	ATCAGGGAACAGGCAGCGT
3443	CGCTGCCTGTTCCCTGATG	CATCAGGGAACAGGCAGCG
3444	GCTGCCTGTTCCCTGATGC	GCATCAGGGAACAGGCAGC
3445	CTGCCTGTTCCCTGATGCT	AGCATCAGGGAACAGGCAG
3446	TGCCTGTTCCCTGATGCTG	CAGCATCAGGGAACAGGCA
3447	GCCTGTTCCCTGATGCTGA	TCAGCATCAGGGAACAGGC
3448	CCTGTTCCCTGATGCTGAC	GTCAGCATCAGGGAACAGG
3449	CTGTTCCCTGATGCTGACC	GGTCAGCATCAGGGAACAG
3450	TGTTCCCTGATGCTGACCC	GGGTCAGCATCAGGGAACA
3451	GTTCCCTGATGCTGACCCA	TGGGTCAGCATCAGGGAAC
3452	TTCCCTGATGCTGACCCAG	CTGGGTCAGCATCAGGGAA
3453	TCCCTGATGCTGACCCAGT	ACTGGGTCAGCATCAGGGA
3454	CCCTGATGCTGACCCAGTT	AACTGGGTCAGCATCAGGG
3455	CCTGATGCTGACCCAGTTT	AAACTGGGTCAGCATCAGG
3456	CTGATGCTGACCCAGTTTG	CAAACTGGGTCAGCATCAG
3457	TGATGCTGACCCAGTTTGT	ACAAACTGGGTCAGCATCA
3458	GATGCTGACCCAGTTTGTC	GACAAACTGGGTCAGCATC
3459	ATGCTGACCCAGTTTGTCT	AGACAAACTGGGTCAGCAT
3460	TGCTGACCCAGTTTGTCTC	GAGACAAACTGGGTCAGCA
3461	GCTGACCCAGTTTGTCTCC	GGAGACAAACTGGGTCAGC
3462	CTGACCCAGTTTGTCTCCA	TGGAGACAAACTGGGTCAG
3463	TGACCCAGTTTGTCTCCAG	CTGGAGACAAACTGGGTCA
3464	GACCCAGTTTGTCTCCAGC	GCTGGAGACAAACTGGGTC
3465	ACCCAGTTTGTCTCCAGCC	GGCTGGAGACAAACTGGGT
3466	CCCAGTTTGTCTCCAGCCA	TGGCTGGAGACAAACTGGG
3467	CCAGTTTGTCTCCAGCCAG	CTGGCTGGAGACAAACTGG
3468	CAGTTTGTCTCCAGCCAGG	CCTGGCTGGAGACAAACTG
3469	AGTTTGTCTCCAGCCAGGC	GCCTGGCTGGAGACAAACT
3470	GTTTGTCTCCAGCCAGGCT	AGCCTGGCTGGAGACAAAC
3471	TTTGTCTCCAGCCAGGCTT	AAGCCTGGCTGGAGACAAA
3472	TTGTCTCCAGCCAGGCTTT	AAAGCCTGGCTGGAGACAA
3473	TGTCTCCAGCCAGGCTTTG	CAAAGCCTGGCTGGAGACA
3474	GTCTCCAGCCAGGCTTTGG	CCAAAGCCTGGCTGGAGAC
3475	TCTCCAGCCAGGCTTTGGC	GCCAAAGCCTGGCTGGAGA
3476	CTCCAGCCAGGCTTTGGCA	TGCCAAAGCCTGGCTGGAG
3477	TCCAGCCAGGCTTTGGCAG	CTGCCAAAGCCTGGCTGGA
3478	CCAGCCAGGCTTTGGCAGA	TCTGCCAAAGCCTGGCTGG
3479	CAGCCAGGCTTTGGCAGAG	CTCTGCCAAAGCCTGGCTG
3480	AGCCAGGCTTTGGCAGAGC	GCTCTGCCAAAGCCTGGCT
3481	GCCAGGCTTTGGCAGAGCT	AGCTCTGCCAAAGCCTGGC
3482	CCAGGCTTTGGCAGAGCTG	CAGCTCTGCCAAAGCCTGG
3483	CAGGCTTTGGCAGAGCTGA	TCAGCTCTGCCAAAGCCTG
3484	AGGCTTTGGCAGAGCTGAG	CTCAGCTCTGCCAAAGCCT
3485	GGCTTTGGCAGAGCTGAGC	GCTCAGCTCTGCCAAAGCC
3486	GCTTTGGCAGAGCTGAGCA	TGCTCAGCTCTGCCAAAGC
3487	CTTTGGCAGAGCTGAGCAC	GTGCTCAGCTCTGCCAAAG
3488	TTTGGCAGAGCTGAGCACT	AGTGCTCAGCTCTGCCAAA
3489	TTGGCAGAGCTGAGCACTG	CAGTGCTCAGCTCTGCCAA
3490	TGGCAGAGCTGAGCACTGC	GCAGTGCTCAGCTCTGCCA
3491	GGCAGAGCTGAGCACTGCA	TGCAGTGCTCAGCTCTGCC
3492	GCAGAGCTGAGCACTGCAA	TTGCAGTGCTCAGCTCTGC
3493	CAGAGCTGAGCACTGCAAT	ATTGCAGTGCTCAGCTCTG
3494	AGAGCTGAGCACTGCAATG	CATTGCAGTGCTCAGCTCT
3495	GAGCTGAGCACTGCAATGC	GCATTGCAGTGCTCAGCTC
3496	AGCTGAGCACTGCAATGCA	TGCATTGCAGTGCTCAGCT
3497	GCTGAGCACTGCAATGCAC	GTGCATTGCAGTGCTCAGC
3498	CTGAGCACTGCAATGCACC	GGTGCATTGCAGTGCTCAG
3499	TGAGCACTGCAATGCACCA	TGGTGCATTGCAGTGCTCA
3500	GAGCACTGCAATGCACCAG	CTGGTGCATTGCAGTGCTC
3501	AGCACTGCAATGCACCAGG	CCTGGTGCATTGCAGTGCT
3502	GCACTGCAATGCACCAGGT	ACCTGGTGCATTGCAGTGC
3503	CACTGCAATGCACCAGGTC	GACCTGGTGCATTGCAGTG
3504	ACTGCAATGCACCAGGTCT	AGACCTGGTGCATTGCAGT
3505	CTGCAATGCACCAGGTCTG	CAGACCTGGTGCATTGCAG
3506	TGCAATGCACCAGGTCTGG	CCAGACCTGGTGCATTGCA
3507	GCAATGCACCAGGTCTGGG	CCCAGACCTGGTGCATTGC
3508	CAATGCACCAGGTCTGGGT	ACCCAGACCTGGTGCATTG
3509	AATGCACCAGGTCTGGGTC	GACCCAGACCTGGTGCATT
3510	ATGCACCAGGTCTGGGTCA	TGACCCAGACCTGGTGCAT
3511	TGCACCAGGTCTGGGTCAA	TTGACCCAGACCTGGTGCA
3512	GCACCAGGTCTGGGTCAAG	CTTGACCCAGACCTGGTGC
3513	CACCAGGTCTGGGTCAAGT	ACTTGACCCAGACCTGGTG
3514	ACCAGGTCTGGGTCAAGTT	AACTTGACCCAGACCTGGT
3515	CCAGGTCTGGGTCAAGTTT	AAACTTGACCCAGACCTGG
3516	CAGGTCTGGGTCAAGTTTG	CAAACTTGACCCAGACCTG
3517	AGGTCTGGGTCAAGTTTGA	TCAAACTTGACCCAGACCT
3518	GGTCTGGGTCAAGTTTGAT	ATCAAACTTGACCCAGACC
3519	GTCTGGGTCAAGTTTGATA	TATCAAACTTGACCCAGAC
3520	TCTGGGTCAAGTTTGATAT	ATATCAAACTTGACCCAGA
3521	CTGGGTCAAGTTTGATATC	GATATCAAACTTGACCCAG
3522	TGGGTCAAGTTTGATATCC	GGATATCAAACTTGACCCA
3523	GGGTCAAGTTTGATATCCG	CGGATATCAAACTTGACCC
3524	GGTCAAGTTTGATATCCGG	CCGGATATCAAACTTGACC
3525	GTCAAGTTTGATATCCGGG	CCCGGATATCAAACTTGAC
3526	TCAAGTTTGATATCCGGGG	CCCCGGATATCAAACTTGA
3527	CAAGTTTGATATCCGGGGG	CCCCCGGATATCAAACTTG
3528	AAGTTTGATATCCGGGGGC	GCCCCCGGATATCAAACTT
3529	AGTTTGATATCCGGGGGCA	TGCCCCCGGATATCAAACT
3530	GTTTGATATCCGGGGGCAC	GTGCCCCCGGATATCAAAC
3531	TTTGATATCCGGGGGCACT	AGTGCCCCCGGATATCAAA
3532	TTGATATCCGGGGGCACTG	CAGTGCCCCCGGATATCAA
3533	TGATATCCGGGGGCACTGC	GCAGTGCCCCCGGATATCA
3534	GATATCCGGGGGCACTGCC	GGCAGTGCCCCCGGATATC
3535	ATATCCGGGGGCACTGCCC	GGGCAGTGCCCCCGGATAT
3536	TATCCGGGGGCACTGCCCC	GGGGCAGTGCCCCCGGATA
3537	ATCCGGGGGCACTGCCCCT	AGGGGCAGTGCCCCCGGAT
3538	TCCGGGGGCACTGCCCCTG	CAGGGGCAGTGCCCCCGGA
3539	CCGGGGGCACTGCCCCTGC	GCAGGGGCAGTGCCCCCGG
3540	CGGGGGCACTGCCCCTGCC	GGCAGGGGCAGTGCCCCCG
3541	GGGGGCACTGCCCCTGCCA	TGGCAGGGGCAGTGCCCCC
3542	GGGGCACTGCCCCTGCCAA	TTGGCAGGGGCAGTGCCCC
3543	GGGCACTGCCCCTGCCAAG	CTTGGCAGGGGCAGTGCCC
3544	GGCACTGCCCCTGCCAAGC	GCTTGGCAGGGGCAGTGCC
3545	GCACTGCCCCTGCCAAGCT	AGCTTGGCAGGGGCAGTGC
3546	CACTGCCCCTGCCAAGCTG	CAGCTTGGCAGGGGCAGTG
3547	ACTGCCCCTGCCAAGCTGA	TCAGCTTGGCAGGGGCAGT
3548	CTGCCCCTGCCAAGCTGAT	ATCAGCTTGGCAGGGGCAG
3549	TGCCCCTGCCAAGCTGATG	CATCAGCTTGGCAGGGGCA
3550	GCCCCTGCCAAGCTGATGC	GCATCAGCTTGGCAGGGGC
3551	CCCCTGCCAAGCTGATGCC	GGCATCAGCTTGGCAGGGG
3552	CCCTGCCAAGCTGATGCCC	GGGCATCAGCTTGGCAGGG
3553	CCTGCCAAGCTGATGCCCG	CGGGCATCAGCTTGGCAGG
3554	CTGCCAAGCTGATGCCCGG	CCGGGCATCAGCTTGGCAG
3555	TGCCAAGCTGATGCCCGGG	CCCGGGCATCAGCTTGGCA
3556	GCCAAGCTGATGCCCGGGT	ACCCGGGCATCAGCTTGGC
3557	CCAAGCTGATGCCCGGGTA	TACCCGGGCATCAGCTTGG
3558	CAAGCTGATGCCCGGGTAT	ATACCCGGGCATCAGCTTG
3559	AAGCTGATGCCCGGGTATG	CATACCCGGGCATCAGCTT
3560	AGCTGATGCCCGGGTATGG	CCATACCCGGGCATCAGCT
3561	GCTGATGCCCGGGTATGGG	CCCATACCCGGGCATCAGC
3562	CTGATGCCCGGGTATGGGC	GCCCATACCCGGGCATCAG
3563	TGATGCCCGGGTATGGGCC	GGCCCATACCCGGGCATCA
3564	GATGCCCGGGTATGGGCCC	GGGCCCATACCCGGGCATC
3565	ATGCCCGGGTATGGGCCCC	GGGGCCCATACCCGGGCAT
3566	TGCCCGGGTATGGGCCCCC	GGGGGCCCATACCCGGGCA
3567	GCCCGGGTATGGGCCCCCG	CGGGGGCCCATACCCGGGC
3568	CCCGGGTATGGGCCCCCGG	CCGGGGGCCCATACCCGGG
3569	CCGGGTATGGGCCCCCGGG	CCCGGGGGCCCATACCCGG
3570	CGGGTATGGGCCCCCGGGG	CCCCGGGGGCCCATACCCG
3571	GGGTATGGGCCCCCGGGGA	TCCCCGGGGGCCCATACCC
3572	GGTATGGGCCCCCGGGGAT	ATCCCCGGGGGCCCATACC
3573	GTATGGGCCCCCGGGGATG	CATCCCCGGGGGCCCATAC
3574	TATGGGCCCCCGGGGATGC	GCATCCCCGGGGGCCCATA
3575	ATGGGCCCCCGGGGATGCA	TGCATCCCCGGGGGCCCAT
3576	TGGGCCCCCGGGGATGCAG	CTGCATCCCCGGGGGCCCA
3577	GGGCCCCCGGGGATGCAGG	CCTGCATCCCCGGGGGCCC
3578	GGCCCCCGGGGATGCAGGC	GCCTGCATCCCCGGGGGCC
3579	GCCCCCGGGGATGCAGGCC	GGCCTGCATCCCCGGGGGC
3580	CCCCCGGGGATGCAGGCCA	TGGCCTGCATCCCCGGGGG
3581	CCCCGGGGATGCAGGCCAG	CTGGCCTGCATCCCCGGGG
3582	CCCGGGGATGCAGGCCAGC	GCTGGCCTGCATCCCCGGG
3583	CCGGGGATGCAGGCCAGCA	TGCTGGCCTGCATCCCCGG
3584	CGGGGATGCAGGCCAGCAG	CTGCTGGCCTGCATCCCCG
3585	GGGGATGCAGGCCAGCAGA	TCTGCTGGCCTGCATCCCC
3586	GGGATGCAGGCCAGCAGAA	TTCTGCTGGCCTGCATCCC
3587	GGATGCAGGCCAGCAGAAG	CTTCTGCTGGCCTGCATCC
3588	GATGCAGGCCAGCAGAAGG	CCTTCTGCTGGCCTGCATC
3589	ATGCAGGCCAGCAGAAGGA	TCCTTCTGCTGGCCTGCAT
3590	TGCAGGCCAGCAGAAGGAA	TTCCTTCTGCTGGCCTGCA
3591	GCAGGCCAGCAGAAGGAAT	ATTCCTTCTGCTGGCCTGC
3592	CAGGCCAGCAGAAGGAATC	GATTCCTTCTGCTGGCCTG
3593	AGGCCAGCAGAAGGAATCA	TGATTCCTTCTGCTGGCCT
3594	GGCCAGCAGAAGGAATCAA	TTGATTCCTTCTGCTGGCC
3595	GCCAGCAGAAGGAATCAAC	GTTGATTCCTTCTGCTGGC
3596	CCAGCAGAAGGAATCAACA	TGTTGATTCCTTCTGCTGG
3597	CAGCAGAAGGAATCAACAC	GTGTTGATTCCTTCTGCTG
3598	AGCAGAAGGAATCAACACA	TGTGTTGATTCCTTCTGCT
3599	GCAGAAGGAATCAACACAG	CTGTGTTGATTCCTTCTGC
3600	CAGAAGGAATCAACACAGA	TCTGTGTTGATTCCTTCTG
3601	AGAAGGAATCAACACAGAA	TTCTGTGTTGATTCCTTCT
3602	GAAGGAATCAACACAGAAA	TTTCTGTGTTGATTCCTTC
3603	AAGGAATCAACACAGAAAA	TTTTCTGTGTTGATTCCTT
3604	AGGAATCAACACAGAAAAC	GTTTTCTGTGTTGATTCCT
3605	GGAATCAACACAGAAAACG	CGTTTTCTGTGTTGATTCC
3606	GAATCAACACAGAAAACGC	GCGTTTTCTGTGTTGATTC
3607	AATCAACACAGAAAACGCC	GGCGTTTTCTGTGTTGATT
3608	ATCAACACAGAAAACGCCC	GGGCGTTTTCTGTGTTGAT
3609	TCAACACAGAAAACGCCCC	GGGGCGTTTTCTGTGTTGA
3610	CAACACAGAAAACGCCCCC	GGGGGCGTTTTCTGTGTTG
3611	AACACAGAAAACGCCCCCA	TGGGGGCGTTTTCTGTGTT
3612	ACACAGAAAACGCCCCCAA	TTGGGGGCGTTTTCTGTGT
3613	CACAGAAAACGCCCCCAAC	GTTGGGGGCGTTTTCTGTG
3614	ACAGAAAACGCCCCCAACT	AGTTGGGGGCGTTTTCTGT
3615	CAGAAAACGCCCCCAACTC	GAGTTGGGGGCGTTTTCTG
3616	AGAAAACGCCCCCAACTCC	GGAGTTGGGGGCGTTTTCT
3617	GAAAACGCCCCCAACTCCA	TGGAGTTGGGGGCGTTTTC
3618	AAAACGCCCCCAACTCCAC	GTGGAGTTGGGGGCGTTTT
3619	AAACGCCCCCAACTCCACA	TGTGGAGTTGGGGGCGTTT
3620	AACGCCCCCAACTCCACAA	TTGTGGAGTTGGGGGCGTT
3621	ACGCCCCCAACTCCACAAC	GTTGTGGAGTTGGGGGCGT
3622	CGCCCCCAACTCCACAACC	GGTTGTGGAGTTGGGGGCG
3623	GCCCCCAACTCCACAACCT	AGGTTGTGGAGTTGGGGGC
3624	CCCCCAACTCCACAACCTT	AAGGTTGTGGAGTTGGGGG
3625	CCCCAACTCCACAACCTTC	GAAGGTTGTGGAGTTGGGG
3626	CCCAACTCCACAACCTTCC	GGAAGGTTGTGGAGTTGGG
3627	CCAACTCCACAACCTTCCT	AGGAAGGTTGTGGAGTTGG
3628	CAACTCCACAACCTTCCTG	CAGGAAGGTTGTGGAGTTG
3629	AACTCCACAACCTTCCTGC	GCAGGAAGGTTGTGGAGTT
3630	ACTCCACAACCTTCCTGCA	TGCAGGAAGGTTGTGGAGT
3631	CTCCACAACCTTCCTGCAA	TTGCAGGAAGGTTGTGGAG
3632	TCCACAACCTTCCTGCAAT	ATTGCAGGAAGGTTGTGGA
3633	CCACAACCTTCCTGCAATG	CATTGCAGGAAGGTTGTGG
3634	CACAACCTTCCTGCAATGG	CCATTGCAGGAAGGTTGTG
3635	ACAACCTTCCTGCAATGGC	GCCATTGCAGGAAGGTTGT
3636	CAACCTTCCTGCAATGGCG	CGCCATTGCAGGAAGGTTG
3637	AACCTTCCTGCAATGGCGA	TCGCCATTGCAGGAAGGTT
3638	ACCTTCCTGCAATGGCGAC	GTCGCCATTGCAGGAAGGT
3639	CCTTCCTGCAATGGCGACA	TGTCGCCATTGCAGGAAGG
3640	CTTCCTGCAATGGCGACAC	GTGTCGCCATTGCAGGAAG
3641	TTCCTGCAATGGCGACACC	GGTGTCGCCATTGCAGGAA
3642	TCCTGCAATGGCGACACCC	GGGTGTCGCCATTGCAGGA
3643	CCTGCAATGGCGACACCCA	TGGGTGTCGCCATTGCAGG
3644	CTGCAATGGCGACACCCAC	GTGGGTGTCGCCATTGCAG
3645	TGCAATGGCGACACCCACA	TGTGGGTGTCGCCATTGCA
3646	GCAATGGCGACACCCACAG	CTGTGGGTGTCGCCATTGC
3647	CAATGGCGACACCCACAGG	CCTGTGGGTGTCGCCATTG
3648	AATGGCGACACCCACAGGA	TCCTGTGGGTGTCGCCATT
3649	ATGGCGACACCCACAGGAC	GTCCTGTGGGTGTCGCCAT
3650	TGGCGACACCCACAGGACC	GGTCCTGTGGGTGTCGCCA
3651	GGCGACACCCACAGGACCA	TGGTCCTGTGGGTGTCGCC
3652	GCGACACCCACAGGACCAA	TTGGTCCTGTGGGTGTCGC
3653	CGACACCCACAGGACCAAG	CTTGGTCCTGTGGGTGTCG
3654	GACACCCACAGGACCAAGA	TCTTGGTCCTGTGGGTGTC
3655	ACACCCACAGGACCAAGAG	CTCTTGGTCCTGTGGGTGT
3656	CACCCACAGGACCAAGAGC	GCTCTTGGTCCTGTGGGTG
3657	ACCCACAGGACCAAGAGCA	TGCTCTTGGTCCTGTGGGT
3658	CCCACAGGACCAAGAGCAT	ATGCTCTTGGTCCTGTGGG
3659	CCACAGGACCAAGAGCATC	GATGCTCTTGGTCCTGTGG
3660	CACAGGACCAAGAGCATCA	TGATGCTCTTGGTCCTGTG
3661	ACAGGACCAAGAGCATCAA	TTGATGCTCTTGGTCCTGT
3662	CAGGACCAAGAGCATCAAA	TTTGATGCTCTTGGTCCTG
3663	AGGACCAAGAGCATCAAAG	CTTTGATGCTCTTGGTCCT
3664	GGACCAAGAGCATCAAAGA	TCTTTGATGCTCTTGGTCC
3665	GACCAAGAGCATCAAAGAG	CTCTTTGATGCTCTTGGTC
3666	ACCAAGAGCATCAAAGAGG	CCTCTTTGATGCTCTTGGT
3667	CCAAGAGCATCAAAGAGGA	TCCTCTTTGATGCTCTTGG
3668	CAAGAGCATCAAAGAGGAG	CTCCTCTTTGATGCTCTTG
3669	AAGAGCATCAAAGAGGAGA	TCTCCTCTTTGATGCTCTT
3670	AGAGCATCAAAGAGGAGAC	GTCTCCTCTTTGATGCTCT
3671	GAGCATCAAAGAGGAGACC	GGTCTCCTCTTTGATGCTC
3672	AGCATCAAAGAGGAGACCC	GGGTCTCCTCTTTGATGCT
3673	GCATCAAAGAGGAGACCCC	GGGGTCTCCTCTTTGATGC
3674	CATCAAAGAGGAGACCCCC	GGGGGTCTCCTCTTTGATG
3675	ATCAAAGAGGAGACCCCCG	CGGGGGTCTCCTCTTTGAT
3676	TCAAAGAGGAGACCCCCGA	TCGGGGGTCTCCTCTTTGA
3677	CAAAGAGGAGACCCCCGAT	ATCGGGGGTCTCCTCTTTG
3678	AAAGAGGAGACCCCCGATT	AATCGGGGGTCTCCTCTTT
3679	AAGAGGAGACCCCCGATTC	GAATCGGGGGTCTCCTCTT
3680	AGAGGAGACCCCCGATTCC	GGAATCGGGGGTCTCCTCT
3681	GAGGAGACCCCCGATTCCG	CGGAATCGGGGGTCTCCTC
3682	AGGAGACCCCCGATTCCGC	GCGGAATCGGGGGTCTCCT
3683	GGAGACCCCCGATTCCGCT	AGCGGAATCGGGGGTCTCC
3684	GAGACCCCCGATTCCGCTG	CAGCGGAATCGGGGGTCTC
3685	AGACCCCCGATTCCGCTGA	TCAGCGGAATCGGGGGTCT
3686	GACCCCCGATTCCGCTGAG	CTCAGCGGAATCGGGGGTC
3687	ACCCCCGATTCCGCTGAGA	TCTCAGCGGAATCGGGGGT
3688	CCCCCGATTCCGCTGAGAC	GTCTCAGCGGAATCGGGGG
3689	CCCCGATTCCGCTGAGACC	GGTCTCAGCGGAATCGGGG
3690	CCCGATTCCGCTGAGACCC	GGGTCTCAGCGGAATCGGG
3691	CCGATTCCGCTGAGACCCC	GGGGTCTCAGCGGAATCGG
3692	CGATTCCGCTGAGACCCCA	TGGGGTCTCAGCGGAATCG
3693	GATTCCGCTGAGACCCCAG	CTGGGGTCTCAGCGGAATC
3694	ATTCCGCTGAGACCCCAGC	GCTGGGGTCTCAGCGGAAT
3695	TTCCGCTGAGACCCCAGCA	TGCTGGGGTCTCAGCGGAA
3696	TCCGCTGAGACCCCAGCAG	CTGCTGGGGTCTCAGCGGA
3697	CCGCTGAGACCCCAGCAGA	TCTGCTGGGGTCTCAGCGG
3698	CGCTGAGACCCCAGCAGAG	CTCTGCTGGGGTCTCAGCG
3699	GCTGAGACCCCAGCAGAGG	CCTCTGCTGGGGTCTCAGC
3700	CTGAGACCCCAGCAGAGGA	TCCTCTGCTGGGGTCTCAG
3701	TGAGACCCCAGCAGAGGAC	GTCCTCTGCTGGGGTCTCA
3702	GAGACCCCAGCAGAGGACC	GGTCCTCTGCTGGGGTCTC
3703	AGACCCCAGCAGAGGACCG	CGGTCCTCTGCTGGGGTCT
3704	GACCCCAGCAGAGGACCGT	ACGGTCCTCTGCTGGGGTC
3705	ACCCCAGCAGAGGACCGTG	CACGGTCCTCTGCTGGGGT
3706	CCCCAGCAGAGGACCGTGC	GCACGGTCCTCTGCTGGGG
3707	CCCAGCAGAGGACCGTGCT	AGCACGGTCCTCTGCTGGG
3708	CCAGCAGAGGACCGTGCTG	CAGCACGGTCCTCTGCTGG
3709	CAGCAGAGGACCGTGCTGG	CCAGCACGGTCCTCTGCTG
3710	AGCAGAGGACCGTGCTGGC	GCCAGCACGGTCCTCTGCT
3711	GCAGAGGACCGTGCTGGCC	GGCCAGCACGGTCCTCTGC
3712	CAGAGGACCGTGCTGGCCG	CGGCCAGCACGGTCCTCTG
3713	AGAGGACCGTGCTGGCCGA	TCGGCCAGCACGGTCCTCT
3714	GAGGACCGTGCTGGCCGAG	CTCGGCCAGCACGGTCCTC
3715	AGGACCGTGCTGGCCGAGG	CCTCGGCCAGCACGGTCCT
3716	GGACCGTGCTGGCCGAGGG	CCCTCGGCCAGCACGGTCC
3717	GACCGTGCTGGCCGAGGGC	GCCCTCGGCCAGCACGGTC
3718	ACCGTGCTGGCCGAGGGCC	GGCCCTCGGCCAGCACGGT
3719	CCGTGCTGGCCGAGGGCCC	GGGCCCTCGGCCAGCACGG
3720	CGTGCTGGCCGAGGGCCCC	GGGGCCCTCGGCCAGCACG
3721	GTGCTGGCCGAGGGCCCCT	AGGGGCCCTCGGCCAGCAC
3722	TGCTGGCCGAGGGCCCCTG	CAGGGGCCCTCGGCCAGCA
3723	GCTGGCCGAGGGCCCCTGC	GCAGGGGCCCTCGGCCAGC
3724	CTGGCCGAGGGCCCCTGCC	GGCAGGGGCCCTCGGCCAG
3725	TGGCCGAGGGCCCCTGCCT	AGGCAGGGGCCCTCGGCCA
3726	GGCCGAGGGCCCCTGCCTT	AAGGCAGGGGCCCTCGGCC
3727	GCCGAGGGCCCCTGCCTTG	CAAGGCAGGGGCCCTCGGC
3728	CCGAGGGCCCCTGCCTTGT	ACAAGGCAGGGGCCCTCGG
3729	CGAGGGCCCCTGCCTTGTC	GACAAGGCAGGGGCCCTCG
3730	GAGGGCCCCTGCCTTGTCC	GGACAAGGCAGGGGCCCTC
3731	AGGGCCCCTGCCTTGTCCT	AGGACAAGGCAGGGGCCCT
3732	GGGCCCCTGCCTTGTCCTT	AAGGACAAGGCAGGGGCCC
3733	GGCCCCTGCCTTGTCCTTC	GAAGGACAAGGCAGGGGCC
3734	GCCCCTGCCTTGTCCTTCT	AGAAGGACAAGGCAGGGGC
3735	CCCCTGCCTTGTCCTTCTC	GAGAAGGACAAGGCAGGGG
3736	CCCTGCCTTGTCCTTCTCT	AGAGAAGGACAAGGCAGGG
3737	CCTGCCTTGTCCTTCTCTC	GAGAGAAGGACAAGGCAGG
3738	CTGCCTTGTCCTTCTCTCT	AGAGAGAAGGACAAGGCAG
3739	TGCCTTGTCCTTCTCTCTG	CAGAGAGAAGGACAAGGCA
3740	GCCTTGTCCTTCTCTCTGC	GCAGAGAGAAGGACAAGGC
3741	CCTTGTCCTTCTCTCTGCG	CGCAGAGAGAAGGACAAGG
3742	CTTGTCCTTCTCTCTGCGA	TCGCAGAGAGAAGGACAAG
3743	TTGTCCTTCTCTCTGCGAA	TTCGCAGAGAGAAGGACAA
3744	TGTCCTTCTCTCTGCGAAC	GTTCGCAGAGAGAAGGACA
3745	GTCCTTCTCTCTGCGAACT	AGTTCGCAGAGAGAAGGAC
3746	TCCTTCTCTCTGCGAACTG	CAGTTCGCAGAGAGAAGGA
3747	CCTTCTCTCTGCGAACTGC	GCAGTTCGCAGAGAGAAGG
3748	CTTCTCTCTGCGAACTGCT	AGCAGTTCGCAGAGAGAAG
3749	TTCTCTCTGCGAACTGCTG	CAGCAGTTCGCAGAGAGAA
3750	TCTCTCTGCGAACTGCTGG	CCAGCAGTTCGCAGAGAGA
3751	CTCTCTGCGAACTGCTGGC	GCCAGCAGTTCGCAGAGAG
3752	TCTCTGCGAACTGCTGGCT	AGCCAGCAGTTCGCAGAGA
3753	CTCTGCGAACTGCTGGCTT	AAGCCAGCAGTTCGCAGAG
3754	TCTGCGAACTGCTGGCTTC	GAAGCCAGCAGTTCGCAGA
3755	CTGCGAACTGCTGGCTTCT	AGAAGCCAGCAGTTCGCAG
3756	TGCGAACTGCTGGCTTCTA	TAGAAGCCAGCAGTTCGCA
3757	GCGAACTGCTGGCTTCTAC	GTAGAAGCCAGCAGTTCGC
3758	CGAACTGCTGGCTTCTACC	GGTAGAAGCCAGCAGTTCG
3759	GAACTGCTGGCTTCTACCG	CGGTAGAAGCCAGCAGTTC
3760	AACTGCTGGCTTCTACCGC	GCGGTAGAAGCCAGCAGTT
3761	ACTGCTGGCTTCTACCGCG	CGCGGTAGAAGCCAGCAGT
3762	CTGCTGGCTTCTACCGCGG	CCGCGGTAGAAGCCAGCAG
3763	TGCTGGCTTCTACCGCGGT	ACCGCGGTAGAAGCCAGCA
3764	GCTGGCTTCTACCGCGGTC	GACCGCGGTAGAAGCCAGC
3765	CTGGCTTCTACCGCGGTCA	TGACCGCGGTAGAAGCCAG
3766	TGGCTTCTACCGCGGTCAA	TTGACCGCGGTAGAAGCCA
3767	GGCTTCTACCGCGGTCAAA	TTTGACCGCGGTAGAAGCC
3768	GCTTCTACCGCGGTCAAAC	GTTTGACCGCGGTAGAAGC
3769	CTTCTACCGCGGTCAAACT	AGTTTGACCGCGGTAGAAG
3770	TTCTACCGCGGTCAAACTC	GAGTTTGACCGCGGTAGAA
3771	TCTACCGCGGTCAAACTCT	AGAGTTTGACCGCGGTAGA
3772	CTACCGCGGTCAAACTCTG	CAGAGTTTGACCGCGGTAG
3773	TACCGCGGTCAAACTCTGC	GCAGAGTTTGACCGCGGTA
3774	ACCGCGGTCAAACTCTGCT	AGCAGAGTTTGACCGCGGT
3775	CCGCGGTCAAACTCTGCTT	AAGCAGAGTTTGACCGCGG
3776	CGCGGTCAAACTCTGCTTG	CAAGCAGAGTTTGACCGCG
3777	GCGGTCAAACTCTGCTTGG	CCAAGCAGAGTTTGACCGC
3778	CGGTCAAACTCTGCTTGGG	CCCAAGCAGAGTTTGACCG
3779	GGTCAAACTCTGCTTGGGC	GCCCAAGCAGAGTTTGACC
3780	GTCAAACTCTGCTTGGGCC	GGCCCAAGCAGAGTTTGAC
3781	TCAAACTCTGCTTGGGCCA	TGGCCCAAGCAGAGTTTGA
3782	CAAACTCTGCTTGGGCCAT	ATGGCCCAAGCAGAGTTTG
3783	AAACTCTGCTTGGGCCATG	CATGGCCCAAGCAGAGTTT
3784	AACTCTGCTTGGGCCATGA	TCATGGCCCAAGCAGAGTT
3785	ACTCTGCTTGGGCCATGAG	CTCATGGCCCAAGCAGAGT
3786	CTCTGCTTGGGCCATGAGC	GCTCATGGCCCAAGCAGAG
3787	TCTGCTTGGGCCATGAGCG	CGCTCATGGCCCAAGCAGA
3788	CTGCTTGGGCCATGAGCGA	TCGCTCATGGCCCAAGCAG
3789	TGCTTGGGCCATGAGCGAA	TTCGCTCATGGCCCAAGCA
3790	GCTTGGGCCATGAGCGAAT	ATTCGCTCATGGCCCAAGC
3791	CTTGGGCCATGAGCGAATA	TATTCGCTCATGGCCCAAG
3792	TTGGGCCATGAGCGAATAC	GTATTCGCTCATGGCCCAA
3793	TGGGCCATGAGCGAATACA	TGTATTCGCTCATGGCCCA
3794	GGGCCATGAGCGAATACAC	GTGTATTCGCTCATGGCCC
3795	GGCCATGAGCGAATACACA	TGTGTATTCGCTCATGGCC
3796	GCCATGAGCGAATACACAT	ATGTGTATTCGCTCATGGC
3797	CCATGAGCGAATACACATG	CATGTGTATTCGCTCATGG
3798	CATGAGCGAATACACATGG	CCATGTGTATTCGCTCATG
3799	ATGAGCGAATACACATGGC	GCCATGTGTATTCGCTCAT
3800	TGAGCGAATACACATGGCC	GGCCATGTGTATTCGCTCA
3801	GAGCGAATACACATGGCCT	AGGCCATGTGTATTCGCTC
3802	AGCGAATACACATGGCCTT	AAGGCCATGTGTATTCGCT
3803	GCGAATACACATGGCCTTC	GAAGGCCATGTGTATTCGC
3804	CGAATACACATGGCCTTCG	CGAAGGCCATGTGTATTCG
3805	GAATACACATGGCCTTCGC	GCGAAGGCCATGTGTATTC
3806	AATACACATGGCCTTCGCC	GGCGAAGGCCATGTGTATT
3807	ATACACATGGCCTTCGCCC	GGGCGAAGGCCATGTGTAT
3808	TACACATGGCCTTCGCCCC	GGGGCGAAGGCCATGTGTA
3809	ACACATGGCCTTCGCCCCC	GGGGGCGAAGGCCATGTGT
3810	CACATGGCCTTCGCCCCCG	CGGGGGCGAAGGCCATGTG
3811	ACATGGCCTTCGCCCCCGT	ACGGGGGCGAAGGCCATGT
3812	CATGGCCTTCGCCCCCGTC	GACGGGGGCGAAGGCCATG
3813	ATGGCCTTCGCCCCCGTCA	TGACGGGGGCGAAGGCCAT
3814	TGGCCTTCGCCCCCGTCAC	GTGACGGGGGCGAAGGCCA
3815	GGCCTTCGCCCCCGTCACT	AGTGACGGGGGCGAAGGCC
3816	GCCTTCGCCCCCGTCACTC	GAGTGACGGGGGCGAAGGC
3817	CCTTCGCCCCCGTCACTCC	GGAGTGACGGGGGCGAAGG
3818	CTTCGCCCCCGTCACTCCG	CGGAGTGACGGGGGCGAAG
3819	TTCGCCCCCGTCACTCCGG	CCGGAGTGACGGGGGCGAA
3820	TCGCCCCCGTCACTCCGGC	GCCGGAGTGACGGGGGCGA
3821	CGCCCCCGTCACTCCGGCC	GGCCGGAGTGACGGGGGCG
3822	GCCCCCGTCACTCCGGCCC	GGGCCGGAGTGACGGGGGC
3823	CCCCCGTCACTCCGGCCCT	AGGGCCGGAGTGACGGGGG
3824	CCCCGTCACTCCGGCCCTG	CAGGGCCGGAGTGACGGGG
3825	CCCGTCACTCCGGCCCTGC	GCAGGGCCGGAGTGACGGG
3826	CCGTCACTCCGGCCCTGCC	GGCAGGGCCGGAGTGACGG
3827	CGTCACTCCGGCCCTGCCC	GGGCAGGGCCGGAGTGACG
3828	GTCACTCCGGCCCTGCCCA	TGGGCAGGGCCGGAGTGAC
3829	TCACTCCGGCCCTGCCCAG	CTGGGCAGGGCCGGAGTGA
3830	CACTCCGGCCCTGCCCAGT	ACTGGGCAGGGCCGGAGTG
3831	ACTCCGGCCCTGCCCAGTG	CACTGGGCAGGGCCGGAGT
3832	CTCCGGCCCTGCCCAGTGA	TCACTGGGCAGGGCCGGAG
3833	TCCGGCCCTGCCCAGTGAT	ATCACTGGGCAGGGCCGGA
3834	CCGGCCCTGCCCAGTGATG	CATCACTGGGCAGGGCCGG
3835	CGGCCCTGCCCAGTGATGA	TCATCACTGGGCAGGGCCG
3836	GGCCCTGCCCAGTGATGAC	GTCATCACTGGGCAGGGCC
3837	GCCCTGCCCAGTGATGACC	GGTCATCACTGGGCAGGGC
3838	CCCTGCCCAGTGATGACCG	CGGTCATCACTGGGCAGGG
3839	CCTGCCCAGTGATGACCGC	GCGGTCATCACTGGGCAGG
3840	CTGCCCAGTGATGACCGCA	TGCGGTCATCACTGGGCAG
3841	TGCCCAGTGATGACCGCAT	ATGCGGTCATCACTGGGCA
3842	GCCCAGTGATGACCGCATC	GATGCGGTCATCACTGGGC
3843	CCCAGTGATGACCGCATCA	TGATGCGGTCATCACTGGG
3844	CCAGTGATGACCGCATCAC	GTGATGCGGTCATCACTGG
3845	CAGTGATGACCGCATCACC	GGTGATGCGGTCATCACTG
3846	AGTGATGACCGCATCACCA	TGGTGATGCGGTCATCACT
3847	GTGATGACCGCATCACCAA	TTGGTGATGCGGTCATCAC
3848	TGATGACCGCATCACCAAC	GTTGGTGATGCGGTCATCA
3849	GATGACCGCATCACCAACA	TGTTGGTGATGCGGTCATC
3850	ATGACCGCATCACCAACAT	ATGTTGGTGATGCGGTCAT
3851	TGACCGCATCACCAACATC	GATGTTGGTGATGCGGTCA
3852	GACCGCATCACCAACATCC	GGATGTTGGTGATGCGGTC
3853	ACCGCATCACCAACATCCT	AGGATGTTGGTGATGCGGT
3854	CCGCATCACCAACATCCTG	CAGGATGTTGGTGATGCGG
3855	CGCATCACCAACATCCTGG	CCAGGATGTTGGTGATGCG
3856	GCATCACCAACATCCTGGA	TCCAGGATGTTGGTGATGC
3857	CATCACCAACATCCTGGAC	GTCCAGGATGTTGGTGATG
3858	ATCACCAACATCCTGGACA	TGTCCAGGATGTTGGTGAT
3859	TCACCAACATCCTGGACAG	CTGTCCAGGATGTTGGTGA
3860	CACCAACATCCTGGACAGC	GCTGTCCAGGATGTTGGTG
3861	ACCAACATCCTGGACAGCA	TGCTGTCCAGGATGTTGGT
3862	CCAACATCCTGGACAGCAT	ATGCTGTCCAGGATGTTGG
3863	CAACATCCTGGACAGCATT	AATGCTGTCCAGGATGTTG
3864	AACATCCTGGACAGCATTA	TAATGCTGTCCAGGATGTT
3865	ACATCCTGGACAGCATTAT	ATAATGCTGTCCAGGATGT
3866	CATCCTGGACAGCATTATC	GATAATGCTGTCCAGGATG
3867	ATCCTGGACAGCATTATCG	CGATAATGCTGTCCAGGAT
3868	TCCTGGACAGCATTATCGC	GCGATAATGCTGTCCAGGA
3869	CCTGGACAGCATTATCGCA	TGCGATAATGCTGTCCAGG
3870	CTGGACAGCATTATCGCAC	GTGCGATAATGCTGTCCAG
3871	TGGACAGCATTATCGCACA	TGTGCGATAATGCTGTCCA
3872	GGACAGCATTATCGCACAG	CTGTGCGATAATGCTGTCC
3873	GACAGCATTATCGCACAGG	CCTGTGCGATAATGCTGTC
3874	ACAGCATTATCGCACAGGT	ACCTGTGCGATAATGCTGT
3875	CAGCATTATCGCACAGGTG	CACCTGTGCGATAATGCTG
3876	AGCATTATCGCACAGGTGG	CCACCTGTGCGATAATGCT
3877	GCATTATCGCACAGGTGGT	ACCACCTGTGCGATAATGC
3878	CATTATCGCACAGGTGGTG	CACCACCTGTGCGATAATG
3879	ATTATCGCACAGGTGGTGG	CCACCACCTGTGCGATAAT
3880	TTATCGCACAGGTGGTGGA	TCCACCACCTGTGCGATAA
3881	TATCGCACAGGTGGTGGAA	TTCCACCACCTGTGCGATA
3882	ATCGCACAGGTGGTGGAAC	GTTCCACCACCTGTGCGAT
3883	TCGCACAGGTGGTGGAACG	CGTTCCACCACCTGTGCGA
3884	CGCACAGGTGGTGGAACGG	CCGTTCCACCACCTGTGCG
3885	GCACAGGTGGTGGAACGGA	TCCGTTCCACCACCTGTGC
3886	CACAGGTGGTGGAACGGAA	TTCCGTTCCACCACCTGTG
3887	ACAGGTGGTGGAACGGAAG	CTTCCGTTCCACCACCTGT
3888	CAGGTGGTGGAACGGAAGA	TCTTCCGTTCCACCACCTG
3889	AGGTGGTGGAACGGAAGAT	ATCTTCCGTTCCACCACCT
3890	GGTGGTGGAACGGAAGATC	GATCTTCCGTTCCACCACC
3891	GTGGTGGAACGGAAGATCC	GGATCTTCCGTTCCACCAC
3892	TGGTGGAACGGAAGATCCA	TGGATCTTCCGTTCCACCA
3893	GGTGGAACGGAAGATCCAG	CTGGATCTTCCGTTCCACC
3894	GTGGAACGGAAGATCCAGG	CCTGGATCTTCCGTTCCAC
3895	TGGAACGGAAGATCCAGGA	TCCTGGATCTTCCGTTCCA
3896	GGAACGGAAGATCCAGGAG	CTCCTGGATCTTCCGTTCC
3897	GAACGGAAGATCCAGGAGA	TCTCCTGGATCTTCCGTTC
3898	AACGGAAGATCCAGGAGAA	TTCTCCTGGATCTTCCGTT
3899	ACGGAAGATCCAGGAGAAA	TTTCTCCTGGATCTTCCGT
3900	CGGAAGATCCAGGAGAAAG	CTTTCTCCTGGATCTTCCG
3901	GGAAGATCCAGGAGAAAGC	GCTTTCTCCTGGATCTTCC
3902	GAAGATCCAGGAGAAAGCC	GGCTTTCTCCTGGATCTTC
3903	AAGATCCAGGAGAAAGCCC	GGGCTTTCTCCTGGATCTT
3904	AGATCCAGGAGAAAGCCCT	AGGGCTTTCTCCTGGATCT
3905	GATCCAGGAGAAAGCCCTG	CAGGGCTTTCTCCTGGATC
3906	ATCCAGGAGAAAGCCCTGG	CCAGGGCTTTCTCCTGGAT
3907	TCCAGGAGAAAGCCCTGGG	CCCAGGGCTTTCTCCTGGA
3908	CCAGGAGAAAGCCCTGGGG	CCCCAGGGCTTTCTCCTGG
3909	CAGGAGAAAGCCCTGGGGC	GCCCCAGGGCTTTCTCCTG
3910	AGGAGAAAGCCCTGGGGCC	GGCCCCAGGGCTTTCTCCT
3911	GGAGAAAGCCCTGGGGCCG	CGGCCCCAGGGCTTTCTCC
3912	GAGAAAGCCCTGGGGCCGG	CCGGCCCCAGGGCTTTCTC
3913	AGAAAGCCCTGGGGCCGGG	CCCGGCCCCAGGGCTTTCT
3914	GAAAGCCCTGGGGCCGGGG	CCCCGGCCCCAGGGCTTTC
3915	AAAGCCCTGGGGCCGGGGC	GCCCCGGCCCCAGGGCTTT
3916	AAGCCCTGGGGCCGGGGCT	AGCCCCGGCCCCAGGGCTT
3917	AGCCCTGGGGCCGGGGCTT	AAGCCCCGGCCCCAGGGCT
3918	GCCCTGGGGCCGGGGCTTC	GAAGCCCCGGCCCCAGGGC
3919	CCCTGGGGCCGGGGCTTCG	CGAAGCCCCGGCCCCAGGG
3920	CCTGGGGCCGGGGCTTCGA	TCGAAGCCCCGGCCCCAGG
3921	CTGGGGCCGGGGCTTCGAG	CTCGAAGCCCCGGCCCCAG
3922	TGGGGCCGGGGCTTCGAGC	GCTCGAAGCCCCGGCCCCA
3923	GGGGCCGGGGCTTCGAGCT	AGCTCGAAGCCCCGGCCCC
3924	GGGCCGGGGCTTCGAGCTG	CAGCTCGAAGCCCCGGCCC
3925	GGCCGGGGCTTCGAGCTGG	CCAGCTCGAAGCCCCGGCC
3926	GCCGGGGCTTCGAGCTGGC	GCCAGCTCGAAGCCCCGGC
3927	CCGGGGCTTCGAGCTGGCC	GGCCAGCTCGAAGCCCCGG
3928	CGGGGCTTCGAGCTGGCCC	GGGCCAGCTCGAAGCCCCG
3929	GGGGCTTCGAGCTGGCCCG	CGGGCCAGCTCGAAGCCCC
3930	GGGCTTCGAGCTGGCCCGG	CCGGGCCAGCTCGAAGCCC
3931	GGCTTCGAGCTGGCCCGGG	CCCGGGCCAGCTCGAAGCC
3932	GCTTCGAGCTGGCCCGGGT	ACCCGGGCCAGCTCGAAGC
3933	CTTCGAGCTGGCCCGGGTC	GACCCGGGCCAGCTCGAAG
3934	TTCGAGCTGGCCCGGGTCT	AGACCCGGGCCAGCTCGAA
3935	TCGAGCTGGCCCGGGTCTG	CAGACCCGGGCCAGCTCGA
3936	CGAGCTGGCCCGGGTCTGC	GCAGACCCGGGCCAGCTCG
3937	GAGCTGGCCCGGGTCTGCG	CGCAGACCCGGGCCAGCTC
3938	AGCTGGCCCGGGTCTGCGC	GCGCAGACCCGGGCCAGCT
3939	GCTGGCCCGGGTCTGCGCA	TGCGCAGACCCGGGCCAGC
3940	CTGGCCCGGGTCTGCGCAA	TTGCGCAGACCCGGGCCAG
3941	TGGCCCGGGTCTGCGCAAG	CTTGCGCAGACCCGGGCCA
3942	GGCCCGGGTCTGCGCAAGG	CCTTGCGCAGACCCGGGCC
3943	GCCCGGGTCTGCGCAAGGG	CCCTTGCGCAGACCCGGGC
3944	CCCGGGTCTGCGCAAGGGC	GCCCTTGCGCAGACCCGGG
3945	CCGGGTCTGCGCAAGGGCC	GGCCCTTGCGCAGACCCGG
3946	CGGGTCTGCGCAAGGGCCT	AGGCCCTTGCGCAGACCCG
3947	GGGTCTGCGCAAGGGCCTG	CAGGCCCTTGCGCAGACCC
3948	GGTCTGCGCAAGGGCCTGG	CCAGGCCCTTGCGCAGACC
3949	GTCTGCGCAAGGGCCTGGG	CCCAGGCCCTTGCGCAGAC
3950	TCTGCGCAAGGGCCTGGGC	GCCCAGGCCCTTGCGCAGA
3951	CTGCGCAAGGGCCTGGGCC	GGCCCAGGCCCTTGCGCAG
3952	TGCGCAAGGGCCTGGGCCT	AGGCCCAGGCCCTTGCGCA
3953	GCGCAAGGGCCTGGGCCTG	CAGGCCCAGGCCCTTGCGC
3954	CGCAAGGGCCTGGGCCTGC	GCAGGCCCAGGCCCTTGCG
3955	GCAAGGGCCTGGGCCTGCC	GGCAGGCCCAGGCCCTTGC
3956	CAAGGGCCTGGGCCTGCCC	GGGCAGGCCCAGGCCCTTG
3957	AAGGGCCTGGGCCTGCCCC	GGGGCAGGCCCAGGCCCTT
3958	AGGGCCTGGGCCTGCCCCT	AGGGGCAGGCCCAGGCCCT
3959	GGGCCTGGGCCTGCCCCTC	GAGGGGCAGGCCCAGGCCC
3960	GGCCTGGGCCTGCCCCTCT	AGAGGGGCAGGCCCAGGCC
3961	GCCTGGGCCTGCCCCTCTC	GAGAGGGGCAGGCCCAGGC
3962	CCTGGGCCTGCCCCTCTCT	AGAGAGGGGCAGGCCCAGG
3963	CTGGGCCTGCCCCTCTCTC	GAGAGAGGGGCAGGCCCAG
3964	TGGGCCTGCCCCTCTCTCC	GGAGAGAGGGGCAGGCCCA
3965	GGGCCTGCCCCTCTCTCCA	TGGAGAGAGGGGCAGGCCC
3966	GGCCTGCCCCTCTCTCCAG	CTGGAGAGAGGGGCAGGCC
3967	GCCTGCCCCTCTCTCCAGT	ACTGGAGAGAGGGGCAGGC
3968	CCTGCCCCTCTCTCCAGTG	CACTGGAGAGAGGGGCAGG
3969	CTGCCCCTCTCTCCAGTGC	GCACTGGAGAGAGGGGCAG
3970	TGCCCCTCTCTCCAGTGCG	CGCACTGGAGAGAGGGGCA
3971	GCCCCTCTCTCCAGTGCGG	CCGCACTGGAGAGAGGGGC
3972	CCCCTCTCTCCAGTGCGGC	GCCGCACTGGAGAGAGGGG
3973	CCCTCTCTCCAGTGCGGCC	GGCCGCACTGGAGAGAGGG
3974	CCTCTCTCCAGTGCGGCCC	GGGCCGCACTGGAGAGAGG
3975	CTCTCTCCAGTGCGGCCCC	GGGGCCGCACTGGAGAGAG
3976	TCTCTCCAGTGCGGCCCCG	CGGGGCCGCACTGGAGAGA
3977	CTCTCCAGTGCGGCCCCGG	CCGGGGCCGCACTGGAGAG
3978	TCTCCAGTGCGGCCCCGGC	GCCGGGGCCGCACTGGAGA
3979	CTCCAGTGCGGCCCCGGCT	AGCCGGGGCCGCACTGGAG
3980	TCCAGTGCGGCCCCGGCTG	CAGCCGGGGCCGCACTGGA
3981	CCAGTGCGGCCCCGGCTGC	GCAGCCGGGGCCGCACTGG
3982	CAGTGCGGCCCCGGCTGCC	GGCAGCCGGGGCCGCACTG
3983	AGTGCGGCCCCGGCTGCCT	AGGCAGCCGGGGCCGCACT
3984	GTGCGGCCCCGGCTGCCTC	GAGGCAGCCGGGGCCGCAC
3985	TGCGGCCCCGGCTGCCTCC	GGAGGCAGCCGGGGCCGCA
3986	GCGGCCCCGGCTGCCTCCC	GGGAGGCAGCCGGGGCCGC
3987	CGGCCCCGGCTGCCTCCCC	GGGGAGGCAGCCGGGGCCG
3988	GGCCCCGGCTGCCTCCCCC	GGGGGAGGCAGCCGGGGCC
3989	GCCCCGGCTGCCTCCCCCA	TGGGGGAGGCAGCCGGGGC
3990	CCCCGGCTGCCTCCCCCAG	CTGGGGGAGGCAGCCGGGG
3991	CCCGGCTGCCTCCCCCAGG	CCTGGGGGAGGCAGCCGGG
3992	CCGGCTGCCTCCCCCAGGG	CCCTGGGGGAGGCAGCCGG
3993	CGGCTGCCTCCCCCAGGGG	CCCCTGGGGGAGGCAGCCG
3994	GGCTGCCTCCCCCAGGGGC	GCCCCTGGGGGAGGCAGCC
3995	GCTGCCTCCCCCAGGGGCT	AGCCCCTGGGGGAGGCAGC
3996	CTGCCTCCCCCAGGGGCTT	AAGCCCCTGGGGGAGGCAG
3997	TGCCTCCCCCAGGGGCTTT	AAAGCCCCTGGGGGAGGCA
3998	GCCTCCCCCAGGGGCTTTG	CAAAGCCCCTGGGGGAGGC
3999	CCTCCCCCAGGGGCTTTGC	GCAAAGCCCCTGGGGGAGG
4000	CTCCCCCAGGGGCTTTGCT	AGCAAAGCCCCTGGGGGAG
4001	TCCCCCAGGGGCTTTGCTG	CAGCAAAGCCCCTGGGGGA
4002	CCCCCAGGGGCTTTGCTGT	ACAGCAAAGCCCCTGGGGG
4003	CCCCAGGGGCTTTGCTGTG	CACAGCAAAGCCCCTGGGG
4004	CCCAGGGGCTTTGCTGTGG	CCACAGCAAAGCCCCTGGG
4005	CCAGGGGCTTTGCTGTGGC	GCCACAGCAAAGCCCCTGG
4006	CAGGGGCTTTGCTGTGGCT	AGCCACAGCAAAGCCCCTG
4007	AGGGGCTTTGCTGTGGCTG	CAGCCACAGCAAAGCCCCT
4008	GGGGCTTTGCTGTGGCTGC	GCAGCCACAGCAAAGCCCC
4009	GGGCTTTGCTGTGGCTGCA	TGCAGCCACAGCAAAGCCC
4010	GGCTTTGCTGTGGCTGCAG	CTGCAGCCACAGCAAAGCC
4011	GCTTTGCTGTGGCTGCAGG	CCTGCAGCCACAGCAAAGC
4012	CTTTGCTGTGGCTGCAGGA	TCCTGCAGCCACAGCAAAG
4013	TTTGCTGTGGCTGCAGGAG	CTCCTGCAGCCACAGCAAA
4014	TTGCTGTGGCTGCAGGAGC	GCTCCTGCAGCCACAGCAA
4015	TGCTGTGGCTGCAGGAGCC	GGCTCCTGCAGCCACAGCA
4016	GCTGTGGCTGCAGGAGCCC	GGGCTCCTGCAGCCACAGC
4017	CTGTGGCTGCAGGAGCCCC	GGGGCTCCTGCAGCCACAG
4018	TGTGGCTGCAGGAGCCCCA	TGGGGCTCCTGCAGCCACA
4019	GTGGCTGCAGGAGCCCCAG	CTGGGGCTCCTGCAGCCAC
4020	TGGCTGCAGGAGCCCCAGC	GCTGGGGCTCCTGCAGCCA
4021	GGCTGCAGGAGCCCCAGCC	GGCTGGGGCTCCTGCAGCC
4022	GCTGCAGGAGCCCCAGCCT	AGGCTGGGGCTCCTGCAGC
4023	CTGCAGGAGCCCCAGCCTT	AAGGCTGGGGCTCCTGCAG
4024	TGCAGGAGCCCCAGCCTTG	CAAGGCTGGGGCTCCTGCA
4025	GCAGGAGCCCCAGCCTTGC	GCAAGGCTGGGGCTCCTGC
4026	CAGGAGCCCCAGCCTTGCC	GGCAAGGCTGGGGCTCCTG
4027	AGGAGCCCCAGCCTTGCCC	GGGCAAGGCTGGGGCTCCT
4028	GGAGCCCCAGCCTTGCCCT	AGGGCAAGGCTGGGGCTCC
4029	GAGCCCCAGCCTTGCCCTC	GAGGGCAAGGCTGGGGCTC
4030	AGCCCCAGCCTTGCCCTCG	CGAGGGCAAGGCTGGGGCT
4031	GCCCCAGCCTTGCCCTCGG	CCGAGGGCAAGGCTGGGGC
4032	CCCCAGCCTTGCCCTCGGC	GCCGAGGGCAAGGCTGGGG
4033	CCCAGCCTTGCCCTCGGCG	CGCCGAGGGCAAGGCTGGG
4034	CCAGCCTTGCCCTCGGCGT	ACGCCGAGGGCAAGGCTGG
4035	CAGCCTTGCCCTCGGCGTG	CACGCCGAGGGCAAGGCTG
4036	AGCCTTGCCCTCGGCGTGG	CCACGCCGAGGGCAAGGCT
4037	GCCTTGCCCTCGGCGTGGC	GCCACGCCGAGGGCAAGGC
4038	CCTTGCCCTCGGCGTGGCT	AGCCACGCCGAGGGCAAGG
4039	CTTGCCCTCGGCGTGGCTT	AAGCCACGCCGAGGGCAAG
4040	TTGCCCTCGGCGTGGCTTC	GAAGCCACGCCGAGGGCAA
4041	TGCCCTCGGCGTGGCTTCC	GGAAGCCACGCCGAGGGCA
4042	GCCCTCGGCGTGGCTTCCA	TGGAAGCCACGCCGAGGGC
4043	CCCTCGGCGTGGCTTCCAC	GTGGAAGCCACGCCGAGGG
4044	CCTCGGCGTGGCTTCCACC	GGTGGAAGCCACGCCGAGG
4045	CTCGGCGTGGCTTCCACCT	AGGTGGAAGCCACGCCGAG
4046	TCGGCGTGGCTTCCACCTC	GAGGTGGAAGCCACGCCGA
4047	CGGCGTGGCTTCCACCTCT	AGAGGTGGAAGCCACGCCG
4048	GGCGTGGCTTCCACCTCTT	AAGAGGTGGAAGCCACGCC
4049	GCGTGGCTTCCACCTCTTC	GAAGAGGTGGAAGCCACGC
4050	CGTGGCTTCCACCTCTTCC	GGAAGAGGTGGAAGCCACG
4051	GTGGCTTCCACCTCTTCCA	TGGAAGAGGTGGAAGCCAC
4052	TGGCTTCCACCTCTTCCAG	CTGGAAGAGGTGGAAGCCA
4053	GGCTTCCACCTCTTCCAGG	CCTGGAAGAGGTGGAAGCC
4054	GCTTCCACCTCTTCCAGGA	TCCTGGAAGAGGTGGAAGC
4055	CTTCCACCTCTTCCAGGAG	CTCCTGGAAGAGGTGGAAG
4056	TTCCACCTCTTCCAGGAGC	GCTCCTGGAAGAGGTGGAA
4057	TCCACCTCTTCCAGGAGCA	TGCTCCTGGAAGAGGTGGA
4058	CCACCTCTTCCAGGAGCAC	GTGCTCCTGGAAGAGGTGG
4059	CACCTCTTCCAGGAGCACT	AGTGCTCCTGGAAGAGGTG
4060	ACCTCTTCCAGGAGCACTG	CAGTGCTCCTGGAAGAGGT
4061	CCTCTTCCAGGAGCACTGG	CCAGTGCTCCTGGAAGAGG
4062	CTCTTCCAGGAGCACTGGA	TCCAGTGCTCCTGGAAGAG
4063	TCTTCCAGGAGCACTGGAG	CTCCAGTGCTCCTGGAAGA
4064	CTTCCAGGAGCACTGGAGG	CCTCCAGTGCTCCTGGAAG
4065	TTCCAGGAGCACTGGAGGC	GCCTCCAGTGCTCCTGGAA
4066	TCCAGGAGCACTGGAGGCA	TGCCTCCAGTGCTCCTGGA
4067	CCAGGAGCACTGGAGGCAG	CTGCCTCCAGTGCTCCTGG
4068	CAGGAGCACTGGAGGCAGG	CCTGCCTCCAGTGCTCCTG
4069	AGGAGCACTGGAGGCAGGG	CCCTGCCTCCAGTGCTCCT
4070	GGAGCACTGGAGGCAGGGC	GCCCTGCCTCCAGTGCTCC
4071	GAGCACTGGAGGCAGGGCC	GGCCCTGCCTCCAGTGCTC
4072	AGCACTGGAGGCAGGGCCA	TGGCCCTGCCTCCAGTGCT
4073	GCACTGGAGGCAGGGCCAG	CTGGCCCTGCCTCCAGTGC
4074	CACTGGAGGCAGGGCCAGC	GCTGGCCCTGCCTCCAGTG
4075	ACTGGAGGCAGGGCCAGCC	GGCTGGCCCTGCCTCCAGT
4076	CTGGAGGCAGGGCCAGCCT	AGGCTGGCCCTGCCTCCAG
4077	TGGAGGCAGGGCCAGCCTG	CAGGCTGGCCCTGCCTCCA
4078	GGAGGCAGGGCCAGCCTGT	ACAGGCTGGCCCTGCCTCC
4079	GAGGCAGGGCCAGCCTGTG	CACAGGCTGGCCCTGCCTC
4080	AGGCAGGGCCAGCCTGTGT	ACACAGGCTGGCCCTGCCT
4081	GGCAGGGCCAGCCTGTGTT	AACACAGGCTGGCCCTGCC
4082	GCAGGGCCAGCCTGTGTTG	CAACACAGGCTGGCCCTGC
4083	CAGGGCCAGCCTGTGTTGG	CCAACACAGGCTGGCCCTG
4084	AGGGCCAGCCTGTGTTGGT	ACCAACACAGGCTGGCCCT
4085	GGGCCAGCCTGTGTTGGTG	CACCAACACAGGCTGGCCC
4086	GGCCAGCCTGTGTTGGTGT	ACACCAACACAGGCTGGCC
4087	GCCAGCCTGTGTTGGTGTC	GACACCAACACAGGCTGGC
4088	CCAGCCTGTGTTGGTGTCA	TGACACCAACACAGGCTGG
4089	CAGCCTGTGTTGGTGTCAG	CTGACACCAACACAGGCTG
4090	AGCCTGTGTTGGTGTCAGG	CCTGACACCAACACAGGCT
4091	GCCTGTGTTGGTGTCAGGG	CCCTGACACCAACACAGGC
4092	CCTGTGTTGGTGTCAGGGA	TCCCTGACACCAACACAGG
4093	CTGTGTTGGTGTCAGGGAT	ATCCCTGACACCAACACAG
4094	TGTGTTGGTGTCAGGGATC	GATCCCTGACACCAACACA
4095	GTGTTGGTGTCAGGGATCC	GGATCCCTGACACCAACAC
4096	TGTTGGTGTCAGGGATCCA	TGGATCCCTGACACCAACA
4097	GTTGGTGTCAGGGATCCAA	TTGGATCCCTGACACCAAC
4098	TTGGTGTCAGGGATCCAAA	TTTGGATCCCTGACACCAA
4099	TGGTGTCAGGGATCCAAAG	CTTTGGATCCCTGACACCA
4100	GGTGTCAGGGATCCAAAGG	CCTTTGGATCCCTGACACC
4101	GTGTCAGGGATCCAAAGGA	TCCTTTGGATCCCTGACAC
4102	TGTCAGGGATCCAAAGGAC	GTCCTTTGGATCCCTGACA
4103	GTCAGGGATCCAAAGGACA	TGTCCTTTGGATCCCTGAC
4104	TCAGGGATCCAAAGGACAT	ATGTCCTTTGGATCCCTGA
4105	CAGGGATCCAAAGGACATT	AATGTCCTTTGGATCCCTG
4106	AGGGATCCAAAGGACATTG	CAATGTCCTTTGGATCCCT
4107	GGGATCCAAAGGACATTGC	GCAATGTCCTTTGGATCCC
4108	GGATCCAAAGGACATTGCA	TGCAATGTCCTTTGGATCC
4109	GATCCAAAGGACATTGCAG	CTGCAATGTCCTTTGGATC
4110	ATCCAAAGGACATTGCAGG	CCTGCAATGTCCTTTGGAT
4111	TCCAAAGGACATTGCAGGG	CCCTGCAATGTCCTTTGGA
4112	CCAAAGGACATTGCAGGGC	GCCCTGCAATGTCCTTTGG
4113	CAAAGGACATTGCAGGGCA	TGCCCTGCAATGTCCTTTG
4114	AAAGGACATTGCAGGGCAA	TTGCCCTGCAATGTCCTTT
4115	AAGGACATTGCAGGGCAAC	GTTGCCCTGCAATGTCCTT
4116	AGGACATTGCAGGGCAACC	GGTTGCCCTGCAATGTCCT
4117	GGACATTGCAGGGCAACCT	AGGTTGCCCTGCAATGTCC
4118	GACATTGCAGGGCAACCTG	CAGGTTGCCCTGCAATGTC
4119	ACATTGCAGGGCAACCTGT	ACAGGTTGCCCTGCAATGT
4120	CATTGCAGGGCAACCTGTG	CACAGGTTGCCCTGCAATG
4121	ATTGCAGGGCAACCTGTGG	CCACAGGTTGCCCTGCAAT
4122	TTGCAGGGCAACCTGTGGG	CCCACAGGTTGCCCTGCAA
4123	TGCAGGGCAACCTGTGGGG	CCCCACAGGTTGCCCTGCA
4124	GCAGGGCAACCTGTGGGGG	CCCCCACAGGTTGCCCTGC
4125	CAGGGCAACCTGTGGGGGA	TCCCCCACAGGTTGCCCTG
4126	AGGGCAACCTGTGGGGGAC	GTCCCCCACAGGTTGCCCT
4127	GGGCAACCTGTGGGGGACA	TGTCCCCCACAGGTTGCCC
4128	GGCAACCTGTGGGGGACAG	CTGTCCCCCACAGGTTGCC
4129	GCAACCTGTGGGGGACAGA	TCTGTCCCCCACAGGTTGC
4130	CAACCTGTGGGGGACAGAA	TTCTGTCCCCCACAGGTTG
4131	AACCTGTGGGGGACAGAAG	CTTCTGTCCCCCACAGGTT
4132	ACCTGTGGGGGACAGAAGC	GCTTCTGTCCCCCACAGGT
4133	CCTGTGGGGGACAGAAGCT	AGCTTCTGTCCCCCACAGG
4134	CTGTGGGGGACAGAAGCTC	GAGCTTCTGTCCCCCACAG
4135	TGTGGGGGACAGAAGCTCT	AGAGCTTCTGTCCCCCACA
4136	GTGGGGGACAGAAGCTCTT	AAGAGCTTCTGTCCCCCAC
4137	TGGGGGACAGAAGCTCTTG	CAAGAGCTTCTGTCCCCCA
4138	GGGGGACAGAAGCTCTTGG	CCAAGAGCTTCTGTCCCCC
4139	GGGGACAGAAGCTCTTGGG	CCCAAGAGCTTCTGTCCCC
4140	GGGACAGAAGCTCTTGGGG	CCCCAAGAGCTTCTGTCCC
4141	GGACAGAAGCTCTTGGGGC	GCCCCAAGAGCTTCTGTCC
4142	GACAGAAGCTCTTGGGGCA	TGCCCCAAGAGCTTCTGTC
4143	ACAGAAGCTCTTGGGGCAC	GTGCCCCAAGAGCTTCTGT
4144	CAGAAGCTCTTGGGGCACT	AGTGCCCCAAGAGCTTCTG
4145	AGAAGCTGTTGGGGCACTT	AAGTGCCCCAAGAGCTTCT
4146	GAAGCTCTTGGGGCACTTG	CAAGTGCCCCAAGAGCTTC
4147	AAGCTCTTGGGGCACTTGG	CCAAGTGCCCCAAGAGCTT
4148	AGCTCTTGGGGCACTTGGA	TCCAAGTGCCCCAAGAGCT
4149	GCTCTTGGGGCACTTGGAG	CTCCAAGTGCCCCAAGAGC
4150	CTCTTGGGGCACTTGGAGG	CCTCCAAGTGCCCCAAGAG
4151	TCTTGGGGCACTTGGAGGC	GCCTCCAAGTGCCCCAAGA
4152	CTTGGGGCACTTGGAGGCC	GGCCTCCAAGTGCCCCAAG
4153	TTGGGGCACTTGGAGGCCA	TGGCCTCCAAGTGCCCCAA
4154	TGGGGCACTTGGAGGCCAG	CTGGCCTCCAAGTGCCCCA
4155	GGGGCACTTGGAGGCCAGG	CCTGGCCTCCAAGTGCCCC
4156	GGGCACTTGGAGGCCAGGT	ACCTGGCCTCCAAGTGCCC
4157	GGCACTTGGAGGCCAGGTG	CACCTGGCCTCCAAGTGCC
4158	GCACTTGGAGGCCAGGTGC	GCACCTGGCCTCCAAGTGC
4159	CACTTGGAGGCCAGGTGCA	TGCACCTGGCCTCCAAGTG
4160	ACTTGGAGGCCAGGTGCAG	CTGCACCTGGCCTCCAAGT
4161	CTTGGAGGCCAGGTGCAGG	CCTGCACCTGGCCTCCAAG
4162	TTGGAGGCCAGGTGCAGGC	GCCTGCACCTGGCCTCCAA
4163	TGGAGGCCAGGTGCAGGCG	CGCCTGCACCTGGCCTCCA
4164	GGAGGCCAGGTGCAGGCGC	GCGCCTGCACCTGGCCTCC
4165	GAGGCCAGGTGCAGGCGCT	AGCGCCTGCACCTGGCCTC
4166	AGGCCAGGTGCAGGCGCTG	CAGCGCCTGCACCTGGCCT
4167	GGCCAGGTGCAGGCGCTGA	TCAGCGCCTGCACCTGGCC
4168	GCCAGGTGCAGGCGCTGAG	CTCAGCGCCTGCACCTGGC
4169	CCAGGTGCAGGCGCTGAGC	GCTCAGCGCCTGCACCTGG
4170	CAGGTGCAGGCGCTGAGCC	GGCTCAGCGCCTGCACCTG
4171	AGGTGCAGGCGCTGAGCCC	GGGCTCAGCGCCTGCACCT
4172	GGTGCAGGCGCTGAGCCCC	GGGGCTCAGCGCCTGCACC
4173	GTGCAGGCGCTGAGCCCCC	GGGGGCTCAGCGCCTGCAC
4174	TGCAGGCGCTGAGCCCCCT	AGGGGGCTCAGCGCCTGCA
4175	GCAGGCGCTGAGCCCCCTC	GAGGGGGCTCAGCGCCTGC
4176	CAGGCGCTGAGCCCCCTCG	CGAGGGGGCTCAGCGCCTG
4177	AGGCGCTGAGCCCCCTCGG	CCGAGGGGGCTCAGCGCCT
4178	GGCGCTGAGCCCCCTCGGA	TCCGAGGGGGCTCAGCGCC
4179	GCGCTGAGCCCCCTCGGAC	GTCCGAGGGGGCTCAGCGC
4180	CGCTGAGCCCCCTCGGACC	GGTCCGAGGGGGCTCAGCG
4181	GCTGAGCCCCCTCGGACCT	AGGTCCGAGGGGGCTCAGC
4182	CTGAGCCCCCTCGGACCTC	GAGGTCCGAGGGGGCTCAG
4183	TGAGCCCCCTCGGACCTCC	GGAGGTCCGAGGGGGCTCA
4184	GAGCCCCCTCGGACCTCCC	GGGAGGTCCGAGGGGGCTC
4185	AGCCCCCTCGGACCTCCCC	GGGGAGGTCCGAGGGGGCT
4186	GCCCCCTCGGACCTCCCCA	TGGGGAGGTCCGAGGGGGC
4187	CCCCCTCGGACCTCCCCAG	CTGGGGAGGTCCGAGGGGG
4188	CCCCTCGGACCTCCCCAGC	GCTGGGGAGGTCCGAGGGG
4189	CCCTCGGACCTCCCCAGCC	GGCTGGGGAGGTCCGAGGG
4190	CCTCGGACCTCCCCAGCCC	GGGCTGGGGAGGTCCGAGG
4191	CTCGGACCTCCCCAGCCCA	TGGGCTGGGGAGGTCCGAG
4192	TCGGACCTCCCCAGCCCAG	CTGGGCTGGGGAGGTCCGA
4193	CGGACCTCCCCAGCCCAGC	GCTGGGCTGGGGAGGTCCG
4194	GGACCTCCCCAGCCCAGCA	TGCTGGGCTGGGGAGGTCC
4195	GACCTCCCCAGCCCAGCAG	CTGCTGGGCTGGGGAGGTC
4196	ACCTCCCCAGCCCAGCAGC	GCTGCTGGGCTGGGGAGGT
4197	CCTCCCCAGCCCAGCAGCC	GGCTGCTGGGCTGGGGAGG
4198	CTCCCCAGCCCAGCAGCCT	AGGCTGCTGGGCTGGGGAG
4199	TCCCCAGCCCAGCAGCCTG	CAGGCTGCTGGGCTGGGGA
4200	CCCCAGCCCAGCAGCCTGG	CCAGGCTGCTGGGCTGGGG
4201	CCCAGCCCAGCAGCCTGGG	CCCAGGCTGCTGGGCTGGG
4202	CCAGCCCAGCAGCCTGGGC	GCCCAGGCTGCTGGGCTGG
4203	CAGCCCAGCAGCCTGGGCA	TGCCCAGGCTGCTGGGCTG
4204	AGCCCAGCAGCCTGGGCAG	CTGCCCAGGCTGCTGGGCT
4205	GCCCAGCAGCCTGGGCAGC	GCTGCCCAGGCTGCTGGGC
4206	CCCAGCAGCCTGGGCAGCA	TGCTGCCCAGGCTGCTGGG
4207	CCAGCAGCCTGGGCAGCAC	GTGCTGCCCAGGCTGCTGG
4208	CAGCAGCCTGGGCAGCACA	TGTGCTGCCCAGGCTGCTG
4209	AGCAGCCTGGGCAGCACAA	TTGTGCTGCCCAGGCTGCT
4210	GCAGCCTGGGCAGCACAAC	GTTGTGCTGCCCAGGCTGC
4211	CAGCCTGGGCAGCACAACA	TGTTGTGCTGCCCAGGCTG
4212	AGCCTGGGCAGCACAACAT	ATGTTGTGCTGCCCAGGCT
4213	GCCTGGGCAGCACAACATT	AATGTTGTGCTGCCCAGGC
4214	CCTGGGCAGCACAACATTC	GAATGTTGTGCTGCCCAGG
4215	CTGGGCAGCACAACATTCT	AGAATGTTGTGCTGCCCAG
4216	TGGGCAGCACAACATTCTG	CAGAATGTTGTGCTGCCCA
4217	GGGCAGCACAACATTCTGG	CCAGAATGTTGTGCTGCCC
4218	GGCAGCACAACATTCTGGG	CCCAGAATGTTGTGCTGCC
4219	GCAGCACAACATTCTGGGA	TCCCAGAATGTTGTGCTGC
4220	CAGCACAACATTCTGGGAG	CTCCCAGAATGTTGTGCTG
4221	AGCACAACATTCTGGGAGG	CCTCCCAGAATGTTGTGCT
4222	GCACAACATTCTGGGAGGG	CCCTCCCAGAATGTTGTGC
4223	CACAACATTCTGGGAGGGC	GCCCTCCCAGAATGTTGTG
4224	ACAACATTCTGGGAGGGCT	AGCCCTCCCAGAATGTTGT
4225	CAACATTCTGGGAGGGCTT	AAGCCCTCCCAGAATGTTG
4226	AACATTCTGGGAGGGCTTC	GAAGCCCTCCCAGAATGTT
4227	ACATTCTGGGAGGGCTTCT	AGAAGCCCTCCCAGAATGT
4228	CATTCTGGGAGGGCTTCTC	GAGAAGCCCTCCCAGAATG
4229	ATTCTGGGAGGGCTTCTCC	GGAGAAGCCCTCCCAGAAT
4230	TTCTGGGAGGGCTTCTCCT	AGGAGAAGCCCTCCCAGAA
4231	TCTGGGAGGGCTTCTCCTG	CAGGAGAAGCCCTCCCAGA
4232	CTGGGAGGGCTTCTCCTGG	CCAGGAGAAGCCCTCCCAG
4233	TGGGAGGGCTTCTCCTGGC	GCCAGGAGAAGCCCTCCCA
4234	GGGAGGGCTTCTCCTGGCC	GGCCAGGAGAAGCCCTCCC
4235	GGAGGGCTTCTCCTGGCCT	AGGCCAGGAGAAGCCCTCC
4236	GAGGGCTTCTCCTGGCCTG	CAGGCCAGGAGAAGCCCTC
4237	AGGGCTTCTCCTGGCCTGA	TCAGGCCAGGAGAAGCCCT
4238	GGGCTTCTCCTGGCCTGAG	CTCAGGCCAGGAGAAGCCC
4239	GGCTTCTCCTGGCCTGAGC	GCTCAGGCCAGGAGAAGCC
4240	GCTTCTCCTGGCCTGAGCT	AGCTCAGGCCAGGAGAAGC
4241	CTTCTCCTGGCCTGAGCTT	AAGCTCAGGCCAGGAGAAG
4242	TTCTCCTGGCCTGAGCTTC	GAAGCTCAGGCCAGGAGAA
4243	TCTCCTGGCCTGAGCTTCG	CGAAGCTCAGGCCAGGAGA
4244	CTCCTGGCCTGAGCTTCGC	GCGAAGCTCAGGCCAGGAG
4245	TCCTGGCCTGAGCTTCGCC	GGCGAAGCTCAGGCCAGGA
4246	CCTGGCCTGAGCTTCGCCC	GGGCGAAGCTCAGGCCAGG
4247	CTGGCCTGAGCTTCGCCCA	TGGGCGAAGCTCAGGCCAG
4248	TGGCCTGAGCTTCGCCCAA	TTGGGCGAAGCTCAGGCCA
4249	GGCCTGAGCTTCGCCCAAA	TTTGGGCGAAGCTCAGGCC
4250	GCCTGAGCTTCGCCCAAAG	CTTTGGGCGAAGCTCAGGC
4251	CCTGAGCTTCGCCCAAAGT	ACTTTGGGCGAAGCTCAGG
4252	CTGAGCTTCGCCCAAAGTC	GACTTTGGGCGAAGCTCAG
4253	TGAGCTTCGCCCAAAGTCA	TGACTTTGGGCGAAGCTCA
4254	GAGCTTCGCCCAAAGTCAG	CTGACTTTGGGCGAAGCTC
4255	AGCTTCGCCCAAAGTCAGA	TCTGACTTTGGGCGAAGCT
4256	GCTTCGCCCAAAGTCAGAC	GTCTGACTTTGGGCGAAGC
4257	CTTCGCCCAAAGTCAGACG	CGTCTGACTTTGGGCGAAG
4258	TTCGCCCAAAGTCAGACGA	TCGTCTGACTTTGGGCGAA
4259	TCGCCCAAAGTCAGACGAG	CTCGTCTGACTTTGGGCGA
4260	CGCCCAAAGTCAGACGAGG	CCTCGTCTGACTTTGGGCG
4261	GCCCAAAGTCAGACGAGGG	CCCTCGTCTGACTTTGGGC
4262	CCCAAAGTCAGACGAGGGC	GCCCTCGTCTGACTTTGGG
4263	CCAAAGTCAGACGAGGGCT	AGCCCTCGTCTGACTTTGG
4264	CAAAGTCAGACGAGGGCTC	GAGCCCTCGTCTGACTTTG
4265	AAAGTCAGACGAGGGCTCT	AGAGCCCTCGTCTGACTTT
4266	AAGTCAGACGAGGGCTCTG	CAGAGCCCTCGTCTGACTT
4267	AGTCAGACGAGGGCTCTGT	ACAGAGCCCTCGTCTGACT
4268	GTCAGACGAGGGCTCTGTC	GACAGAGCCCTCGTCTGAC
4269	TCAGACGAGGGCTCTGTCC	GGACAGAGCCCTCGTCTGA
4270	CAGACGAGGGCTCTGTCCT	AGGACAGAGCCCTCGTCTG
4271	AGACGAGGGCTCTGTCCTC	GAGGACAGAGCCCTCGTCT
4272	GACGAGGGCTCTGTCCTCC	GGAGGACAGAGCCCTCGTC
4273	ACGAGGGCTCTGTCCTCCT	AGGAGGACAGAGCCCTCGT
4274	CGAGGGCTCTGTCCTCCTG	CAGGAGGACAGAGCCCTCG
4275	GAGGGCTCTGTCCTCCTGC	GCAGGAGGACAGAGCCCTC
4276	AGGGCTCTGTCCTCCTGCT	AGCAGGAGGACAGAGCCCT
4277	GGGCTCTGTCCTCCTGCTG	CAGCAGGAGGACAGAGCCC
4278	GGCTCTGTCCTCCTGCTGC	GCAGCAGGAGGACAGAGCC
4279	GCTCTGTCCTCCTGCTGCA	TGCAGCAGGAGGACAGAGC
4280	CTCTGTCCTCCTGCTGCAC	GTGCAGCAGGAGGACAGAG
4281	TCTGTCCTCCTGCTGCACC	GGTGCAGCAGGAGGACAGA
4282	CTGTCCTCCTGCTGCACCG	CGGTGCAGCAGGAGGACAG
4283	TGTCCTCCTGCTGCACCGA	TCGGTGCAGCAGGAGGACA
4284	GTCCTCCTGCTGCACCGAG	CTCGGTGCAGCAGGAGGAC
4285	TCCTCCTGCTGCACCGAGC	GCTCGGTGCAGCAGGAGGA
4286	CCTCCTGCTGCACCGAGCT	AGCTCGGTGCAGCAGGAGG
4287	CTCCTGCTGCACCGAGCTT	AAGCTCGGTGCAGCAGGAG
4288	TCCTGCTGCACCGAGCTTT	AAAGCTCGGTGCAGCAGGA
4289	CCTGCTGCACCGAGCTTTG	CAAAGCTCGGTGCAGCAGG
4290	CTGCTGCACCGAGCTTTGG	CCAAAGCTCGGTGCAGCAG
4291	TGCTGCACCGAGCTTTGGG	CCCAAAGCTCGGTGCAGCA
4292	GCTGCACCGAGCTTTGGGG	CCCCAAAGCTCGGTGCAGC
4293	CTGCACCGAGCTTTGGGGG	CCCCCAAAGCTCGGTGCAG
4294	TGCACCGAGCTTTGGGGGA	TCCCCCAAAGCTCGGTGCA
4295	GCACCGAGCTTTGGGGGAT	ATCCCCCAAAGCTCGGTGC
4296	CACCGAGCTTTGGGGGATG	CATCCCCCAAAGCTCGGTG
4297	ACCGAGCTTTGGGGGATGA	TCATCCCCCAAAGCTCGGT
4298	CCGAGCTTTGGGGGATGAG	CTCATCCCCCAAAGCTCGG
4299	CGAGCTTTGGGGGATGAGG	CCTCATCCCCCAAAGCTCG
4300	GAGCTTTGGGGGATGAGGA	TCCTCATCCCCCAAAGCTC
4301	AGCTTTGGGGGATGAGGAC	GTCCTCATCCCCCAAAGCT
4302	GCTTTGGGGGATGAGGACA	TGTCCTCATCCCCCAAAGC
4303	CTTTGGGGGATGAGGACAC	GTGTCCTCATCCCCCAAAG
4304	TTTGGGGGATGAGGACACC	GGTGTCCTCATCCCCCAAA
4305	TTGGGGGATGAGGACACCA	TGGTGTCCTCATCCCCCAA
4306	TGGGGGATGAGGACACCAG	CTGGTGTCCTCATCCCCCA
4307	GGGGGATGAGGACACCAGC	GCTGGTGTCCTCATCCCCC
4308	GGGGATGAGGACACCAGCA	TGCTGGTGTCCTCATCCCC
4309	GGGATGAGGACACCAGCAG	CTGCTGGTGTCCTCATCCC
4310	GGATGAGGACACCAGCAGG	CCTGCTGGTGTCCTCATCC
4311	GATGAGGACACCAGCAGGG	CCCTGCTGGTGTCCTCATC
4312	ATGAGGACACCAGCAGGGT	ACCCTGCTGGTGTCCTCAT
4313	TGAGGACACCAGCAGGGTG	CACCCTGCTGGTGTCCTCA
4314	GAGGACACCAGCAGGGTGG	CCACCCTGCTGGTGTCCTC
4315	AGGACACCAGCAGGGTGGA	TCCACCCTGCTGGTGTCCT
4316	GGACACCAGCAGGGTGGAG	CTCCACCCTGCTGGTGTCC
4317	GACACCAGCAGGGTGGAGA	TCTCCACCCTGCTGGTGTC
4318	ACACCAGCAGGGTGGAGAA	TTCTCCACCCTGCTGGTGT
4319	CACCAGCAGGGTGGAGAAC	GTTCTCCACCCTGCTGGTG
4320	ACCAGCAGGGTGGAGAACC	GGTTCTCCACCCTGCTGGT
4321	CCAGCAGGGTGGAGAACCT	AGGTTCTCCACCCTGCTGG
4322	CAGCAGGGTGGAGAACCTA	TAGGTTCTCCACCCTGCTG
4323	AGCAGGGTGGAGAACCTAG	CTAGGTTCTCCACCCTGCT
4324	GCAGGGTGGAGAACCTAGC	GCTAGGTTCTCCACCCTGC
4325	CAGGGTGGAGAACCTAGCT	AGCTAGGTTCTCCACCCTG
4326	AGGGTGGAGAACCTAGCTG	CAGCTAGGTTCTCCACCCT
4327	GGGTGGAGAACCTAGCTGC	GCAGCTAGGTTCTCCACCC
4328	GGTGGAGAACCTAGCTGCC	GGCAGCTAGGTTCTCCACC
4329	GTGGAGAACCTAGCTGCCA	TGGCAGCTAGGTTCTCCAC
4330	TGGAGAACCTAGCTGCCAG	CTGGCAGCTAGGTTCTCCA
4331	GGAGAACCTAGCTGCCAGT	ACTGGCAGCTAGGTTCTCC
4332	GAGAACCTAGCTGCCAGTC	GACTGGCAGCTAGGTTCTC
4333	AGAACCTAGCTGCCAGTCT	AGACTGGCAGCTAGGTTCT
4334	GAACCTAGCTGCCAGTCTG	CAGACTGGCAGCTAGGTTC
4335	AACCTAGCTGCCAGTCTGC	GCAGACTGGCAGCTAGGTT
4336	ACCTAGCTGCCAGTCTGCC	GGCAGACTGGCAGCTAGGT
4337	CCTAGCTGCCAGTCTGCCA	TGGCAGACTGGCAGCTAGG
4338	CTAGCTGCCAGTCTGCCAC	GTGGCAGACTGGCAGCTAG
4339	TAGCTGCCAGTCTGCCACT	AGTGGCAGACTGGCAGCTA
4340	AGCTGCCAGTCTGCCACTT	AAGTGGCAGACTGGCAGCT
4341	GCTGCCAGTCTGCCACTTC	GAAGTGGCAGACTGGCAGC
4342	CTGCCAGTCTGCCACTTCC	GGAAGTGGCAGACTGGCAG
4343	TGCCAGTCTGCCACTTCCG	CGGAAGTGGCAGACTGGCA
4344	GCCAGTCTGCCACTTCCGG	CCGGAAGTGGCAGACTGGC
4345	CCAGTCTGCCACTTCCGGA	TCCGGAAGTGGCAGACTGG
4346	CAGTCTGCCACTTCCGGAG	CTCCGGAAGTGGCAGACTG
4347	AGTCTGCCACTTCCGGAGT	ACTCCGGAAGTGGCAGACT
4348	GTCTGCCACTTCCGGAGTA	TACTCCGGAAGTGGCAGAC
4349	TCTGCCACTTCCGGAGTAC	GTACTCCGGAAGTGGCAGA
4350	CTGCCACTTCCGGAGTACT	AGTACTCCGGAAGTGGCAG
4351	TGCCACTTCCGGAGTACTG	CAGTACTCCGGAAGTGGCA
4352	GCCACTTCCGGAGTACTGC	GCAGTACTCCGGAAGTGGC
4353	CCACTTCCGGAGTACTGCG	CGCAGTACTCCGGAAGTGG
4354	CACTTCCGGAGTACTGCGC	GCGCAGTACTCCGGAAGTG
4355	ACTTCCGGAGTACTGCGCC	GGCGCAGTACTCCGGAAGT
4356	CTTCCGGAGTACTGCGCCC	GGGCGCAGTACTCCGGAAG
4357	TTCCGGAGTACTGCGCCCT	AGGGCGCAGTACTCCGGAA
4358	TCCGGAGTACTGCGCCCTC	GAGGGCGCAGTACTCCGGA
4359	CCGGAGTACTGCGCCCTCC	GGAGGGCGCAGTACTCCGG
4360	CGGAGTACTGCGCCCTCCA	TGGAGGGCGCAGTACTCCG
4361	GGAGTACTGCGCCCTCCAT	ATGGAGGGCGCAGTACTCC
4362	GAGTACTGCGCCCTCCATG	CATGGAGGGCGCAGTACTC
4363	AGTACTGCGCCCTCCATGG	CCATGGAGGGCGCAGTACT
4364	GTACTGCGCCCTCCATGGA	TCCATGGAGGGCGCAGTAC
4365	TACTGCGCCCTCCATGGAA	TTCCATGGAGGGCGCAGTA
4366	ACTGCGCCCTCCATGGAAA	TTTCCATGGAGGGCGCAGT
4367	CTGCGCCCTCCATGGAAAA	TTTTCCATGGAGGGCGCAG
4368	TGCGCCCTCCATGGAAAAC	GTTTTCCATGGAGGGCGCA
4369	GCGCCCTCCATGGAAAACT	AGTTTTCCATGGAGGGCGC
4370	CGCCCTCCATGGAAAACTC	GAGTTTTCCATGGAGGGCG
4371	GCCCTCCATGGAAAACTCA	TGAGTTTTCCATGGAGGGC
4372	CCCTCCATGGAAAACTCAA	TTGAGTTTTCCATGGAGGG
4373	CCTCCATGGAAAACTCAAC	GTTGAGTTTTCCATGGAGG
4374	CTCCATGGAAAACTCAACC	GGTTGAGTTTTCCATGGAG
4375	TCCATGGAAAACTCAACCT	AGGTTGAGTTTTCCATGGA
4376	CCATGGAAAACTCAACCTG	CAGGTTGAGTTTTCCATGG
4377	CATGGAAAACTCAACCTGG	CCAGGTTGAGTTTTCCATG
4378	ATGGAAAACTCAACCTGGC	GCCAGGTTGAGTTTTCCAT
4379	TGGAAAACTCAACCTGGCT	AGCCAGGTTGAGTTTTCCA
4380	GGAAAACTCAACCTGGCTT	AAGCCAGGTTGAGTTTTCC
4381	GAAAACTCAACCTGGCTTC	GAAGCCAGGTTGAGTTTTC
4382	AAAACTCAACCTGGCTTCC	GGAAGCCAGGTTGAGTTTT
4383	AAACTCAACCTGGCTTCCT	AGGAAGCCAGGTTGAGTTT
4384	AACTCAACCTGGCTTCCTA	TAGGAAGCCAGGTTGAGTT
4385	ACTCAACCTGGCTTCCTAC	GTAGGAAGCCAGGTTGAGT
4386	CTCAACCTGGCTTCCTACC	GGTAGGAAGCCAGGTTGAG
4387	TCAACCTGGCTTCCTACCT	AGGTAGGAAGCCAGGTTGA
4388	CAACCTGGCTTCCTACCTC	GAGGTAGGAAGCCAGGTTG
4389	AACCTGGCTTCCTACCTCC	GGAGGTAGGAAGCCAGGTT
4390	ACCTGGCTTCCTACCTCCC	GGGAGGTAGGAAGCCAGGT
4391	CCTGGCTTCCTACCTCCCA	TGGGAGGTAGGAAGCCAGG
4392	CTGGCTTCCTACCTCCCAC	GTGGGAGGTAGGAAGCCAG
4393	TGGCTTCCTACCTCCCACC	GGTGGGAGGTAGGAAGCCA
4394	GGCTTCCTACCTCCCACCG	CGGTGGGAGGTAGGAAGCC
4395	GCTTCCTACCTCCCACCGG	CCGGTGGGAGGTAGGAAGC
4396	CTTCCTACCTCCCACCGGG	CCCGGTGGGAGGTAGGAAG
4397	TTCCTACCTCCCACCGGGC	GCCCGGTGGGAGGTAGGAA
4398	TCCTACCTCCCACCGGGCC	GGCCCGGTGGGAGGTAGGA
4399	CCTACCTCCCACCGGGCCT	AGGCCCGGTGGGAGGTAGG
4400	CTACCTCCCACCGGGCCTT	AAGGCCCGGTGGGAGGTAG
4401	TACCTCCCACCGGGCCTTG	CAAGGCCCGGTGGGAGGTA
4402	ACCTCCCACCGGGCCTTGC	GCAAGGCCCGGTGGGAGGT
4403	CCTCCCACCGGGCCTTGCC	GGCAAGGCCCGGTGGGAGG
4404	CTCCCACCGGGCCTTGCCC	GGGCAAGGCCCGGTGGGAG
4405	TCCCACCGGGCCTTGCCCT	AGGGCAAGGCCCGGTGGGA
4406	CCCACCGGGCCTTGCCCTG	CAGGGCAAGGCCCGGTGGG
4407	CCACCGGGCCTTGCCCTGC	GCAGGGCAAGGCCCGGTGG
4408	CACCGGGCCTTGCCCTGCG	CGCAGGGCAAGGCCCGGTG
4409	ACCGGGCCTTGCCCTGCGT	ACGCAGGGCAAGGCCCGGT
4410	CCGGGCCTTGCCCTGCGTC	GACGCAGGGCAAGGCCCGG
4411	CGGGCCTTGCCCTGCGTCC	GGACGCAGGGCAAGGCCCG
4412	GGGCCTTGCCCTGCGTCCA	TGGACGCAGGGCAAGGCCC
4413	GGCCTTGCCCTGCGTCCAC	GTGGACGCAGGGCAAGGCC
4414	GCCTTGCCCTGCGTCCACT	AGTGGACGCAGGGCAAGGC
4415	CCTTGCCCTGCGTCCACTG	CAGTGGACGCAGGGCAAGG
4416	CTTGCCCTGCGTCCACTGG	CCAGTGGACGCAGGGCAAG
4417	TTGCCCTGCGTCCACTGGA	TCCAGTGGACGCAGGGCAA
4418	TGCCCTGCGTCCACTGGAG	CTCCAGTGGACGCAGGGCA
4419	GCCCTGCGTCCACTGGAGC	GCTCCAGTGGACGCAGGGC
4420	CCCTGCGTCCACTGGAGCC	GGCTCCAGTGGACGCAGGG
4421	CCTGCGTCCACTGGAGCCC	GGGCTCCAGTGGACGCAGG
4422	CTGCGTCCACTGGAGCCCC	GGGGCTCCAGTGGACGCAG
4423	TGCGTCCACTGGAGCCCCA	TGGGGCTCCAGTGGACGCA
4424	GCGTCCACTGGAGCCCCAG	CTGGGGCTCCAGTGGACGC
4425	CGTCCACTGGAGCCCCAGC	GCTGGGGCTCCAGTGGACG
4426	GTCCACTGGAGCCCCAGCT	AGCTGGGGCTCCAGTGGAC
4427	TCCACTGGAGCCCCAGCTC	GAGCTGGGGCTCCAGTGGA
4428	CCACTGGAGCCCCAGCTCT	AGAGCTGGGGCTCCAGTGG
4429	CACTGGAGCCCCAGCTCTG	CAGAGCTGGGGCTCCAGTG
4430	ACTGGAGCCCCAGCTCTGG	CCAGAGCTGGGGCTCCAGT
4431	CTGGAGCCCCAGCTCTGGG	CCCAGAGCTGGGGCTCCAG
4432	TGGAGCCCCAGCTCTGGGC	GCCCAGAGCTGGGGCTCCA
4433	GGAGCCCCAGCTCTGGGCA	TGCCCAGAGCTGGGGCTCC
4434	GAGCCCCAGCTCTGGGCAG	CTGCCCAGAGCTGGGGCTC
4435	AGCCCCAGCTCTGGGCAGC	GCTGCCCAGAGCTGGGGCT
4436	GCCCCAGCTCTGGGCAGCC	GGCTGCCCAGAGCTGGGGC
4437	CCCCAGCTCTGGGCAGCCT	AGGCTGCCCAGAGCTGGGG
4438	CCCAGCTCTGGGCAGCCTA	TAGGCTGCCCAGAGCTGGG
4439	CCAGCTCTGGGCAGCCTAT	ATAGGCTGCCCAGAGCTGG
4440	CAGCTCTGGGCAGCCTATG	CATAGGCTGCCCAGAGCTG
4441	AGCTCTGGGCAGCCTATGG	CCATAGGCTGCCCAGAGCT
4442	GCTCTGGGCAGCCTATGGT	ACCATAGGCTGCCCAGAGC
4443	CTCTGGGCAGCCTATGGTG	CACCATAGGCTGCCCAGAG
4444	TCTGGGCAGCCTATGGTGT	ACACCATAGGCTGCCCAGA
4445	CTGGGCAGCCTATGGTGTG	CACACCATAGGCTGCCCAG
4446	TGGGCAGCCTATGGTGTGA	TCACACCATAGGCTGCCCA
4447	GGGCAGCCTATGGTGTGAG	CTCACACCATAGGCTGCCC
4448	GGCAGCCTATGGTGTGAGC	GCTCACACCATAGGCTGCC
4449	GCAGCCTATGGTGTGAGCC	GGCTCACACCATAGGCTGC
4450	CAGCCTATGGTGTGAGCCC	GGGCTCACACCATAGGCTG
4451	AGCCTATGGTGTGAGCCCG	CGGGCTCACACCATAGGCT
4452	GCCTATGGTGTGAGCCCGC	GCGGGCTCACACCATAGGC
4453	CCTATGGTGTGAGCCCGCA	TGCGGGCTCACACCATAGG
4454	CTATGGTGTGAGCCCGCAC	GTGCGGGCTCACACCATAG
4455	TATGGTGTGAGCCCGCACC	GGTGCGGGCTCACACCATA
4456	ATGGTGTGAGCCCGCACCG	CGGTGCGGGCTCACACCAT
4457	TGGTGTGAGCCCGCACCGG	CCGGTGCGGGCTCACACCA
4458	GGTGTGAGCCCGCACCGGG	CCCGGTGCGGGCTCACACC
4459	GTGTGAGCCCGCACCGGGG	CCCCGGTGCGGGCTCACAC
4460	TGTGAGCCCGCACCGGGGA	TCCCCGGTGCGGGCTCACA
4461	GTGAGCCCGCACCGGGGAC	GTCCCCGGTGCGGGCTCAC
4462	TGAGCCCGCACCGGGGACA	TGTCCCCGGTGCGGGCTCA
4463	GAGCCCGCACCGGGGACAC	GTGTCCCCGGTGCGGGCTC
4464	AGCCCGCACCGGGGACACC	GGTGTCCCCGGTGCGGGCT
4465	GCCCGCACCGGGGACACCT	AGGTGTCCCCGGTGCGGGC
4466	CCCGCACCGGGGACACCTG	CAGGTGTCCCCGGTGCGGG
4467	CCGCACCGGGGACACCTGG	CCAGGTGTCCCCGGTGCGG
4468	CGCACCGGGGACACCTGGG	CCCAGGTGTCCCCGGTGCG
4469	GCACCGGGGACACCTGGGG	CCCCAGGTGTCCCCGGTGC
4470	CACCGGGGACACCTGGGGA	TCCCCAGGTGTCCCCGGTG
4471	ACCGGGGACACCTGGGGAC	GTCCCCAGGTGTCCCCGGT
4472	CCGGGGACACCTGGGGACC	GGTCCCCAGGTGTCCCCGG
4473	CGGGGACACCTGGGGACCA	TGGTCCCCAGGTGTCCCCG
4474	GGGGACACCTGGGGACCAA	TTGGTCCCCAGGTGTCCCC
4475	GGGACACCTGGGGACCAAG	CTTGGTCCCCAGGTGTCCC
4476	GGACACCTGGGGACCAAGA	TCTTGGTCCCCAGGTGTCC
4477	GACACCTGGGGACCAAGAA	TTCTTGGTCCCCAGGTGTC
4478	ACACCTGGGGACCAAGAAC	GTTCTTGGTCCCCAGGTGT
4479	CACCTGGGGACCAAGAACC	GGTTCTTGGTCCCCAGGTG
4480	ACCTGGGGACCAAGAACCT	AGGTTCTTGGTCCCCAGGT
4481	CCTGGGGACCAAGAACCTC	GAGGTTCTTGGTCCCCAGG
4482	CTGGGGACCAAGAACCTCT	AGAGGTTCTTGGTCCCCAG
4483	TGGGGACCAAGAACCTCTG	CAGAGGTTCTTGGTCCCCA
4484	GGGGACCAAGAACCTCTGT	ACAGAGGTTCTTGGTCCCC
4485	GGGACCAAGAACCTCTGTG	CACAGAGGTTCTTGGTCCC
4486	GGACCAAGAACCTCTGTGT	ACACAGAGGTTCTTGGTCC
4487	GACCAAGAACCTCTGTGTG	CACACAGAGGTTCTTGGTC
4488	ACCAAGAACCTCTGTGTGG	CCACACAGAGGTTCTTGGT
4489	CCAAGAACCTCTGTGTGGA	TCCACACAGAGGTTCTTGG
4490	CAAGAACCTCTGTGTGGAG	CTCCACACAGAGGTTCTTG
4491	AAGAACCTCTGTGTGGAGG	CCTCCACACAGAGGTTCTT
4492	AGAACCTCTGTGTGGAGGT	ACCTCCACACAGAGGTTCT
4493	GAACCTCTGTGTGGAGGTG	CACCTCCACACAGAGGTTC
4494	AACCTCTGTGTGGAGGTGG	CCACCTCCACACAGAGGTT
4495	ACCTCTGTGTGGAGGTGGC	GCCACCTCCACACAGAGGT
4496	CCTCTGTGTGGAGGTGGCC	GGCCACCTCCACACAGAGG
4497	CTCTGTGTGGAGGTGGCCG	CGGCCACCTCCACACAGAG
4498	TCTGTGTGGAGGTGGCCGA	TCGGCCACCTCCACACAGA
4499	CTGTGTGGAGGTGGCCGAC	GTCGGCCACCTCCACACAG
4500	TGTGTGGAGGTGGCCGACC	GGTCGGCCACCTCCACACA
4501	GTGTGGAGGTGGCCGACCT	AGGTCGGCCACCTCCACAC
4502	TGTGGAGGTGGCCGACCTG	CAGGTCGGCCACCTCCACA
4503	GTGGAGGTGGCCGACCTGG	CCAGGTCGGCCACCTCCAC
4504	TGGAGGTGGCCGACCTGGT	ACCAGGTCGGCCACCTCCA
4505	GGAGGTGGCCGACCTGGTC	GACCAGGTCGGCCACCTCC
4506	GAGGTGGCCGACCTGGTCA	TGACCAGGTCGGCCACCTC
4507	AGGTGGCCGACCTGGTCAG	CTGACCAGGTCGGCCACCT
4508	GGTGGCCGACCTGGTCAGC	GCTGACCAGGTCGGCCACC
4509	GTGGCCGACCTGGTCAGCA	TGCTGACCAGGTCGGCCAC
4510	TGGCCGACCTGGTCAGCAT	ATGCTGACCAGGTCGGCCA
4511	GGCCGACCTGGTCAGCATC	GATGCTGACCAGGTCGGCC
4512	GCCGACCTGGTCAGCATCC	GGATGCTGACCAGGTCGGC
4513	CCGACCTGGTCAGCATCCT	AGGATGCTGACCAGGTCGG
4514	CGACCTGGTCAGCATCCTG	CAGGATGCTGACCAGGTCG
4515	GACCTGGTCAGCATCCTGG	CCAGGATGCTGACCAGGTC
4516	ACCTGGTCAGCATCCTGGT	ACCAGGATGCTGACCAGGT
4517	CCTGGTCAGCATCCTGGTG	CACCAGGATGCTGACCAGG
4518	CTGGTCAGCATCCTGGTGC	GCACCAGGATGCTGACCAG
4519	TGGTCAGCATCCTGGTGCA	TGCACCAGGATGCTGACCA
4520	GGTCAGCATCCTGGTGCAT	ATGCACCAGGATGCTGACC
4521	GTCAGCATCCTGGTGCATG	CATGCACCAGGATGCTGAC
4522	TCAGCATCCTGGTGCATGC	GCATGCACCAGGATGCTGA
4523	CAGCATCCTGGTGCATGCC	GGCATGCACCAGGATGCTG
4524	AGCATCCTGGTGCATGCCG	CGGCATGCACCAGGATGCT
4525	GCATCCTGGTGCATGCCGA	TCGGCATGCACCAGGATGC
4526	CATCCTGGTGCATGCCGAC	GTCGGCATGCACCAGGATG
4527	ATCCTGGTGCATGCCGACA	TGTCGGCATGCACCAGGAT
4528	TCCTGGTGCATGCCGACAC	GTGTCGGCATGCACCAGGA
4529	CCTGGTGCATGCCGACACA	TGTGTCGGCATGCACCAGG
4530	CTGGTGCATGCCGACACAC	GTGTGTCGGCATGCACCAG
4531	TGGTGCATGCCGACACACC	GGTGTGTCGGCATGCACCA
4532	GGTGCATGCCGACACACCA	TGGTGTGTCGGCATGCACC
4533	GTGCATGCCGACACACCAC	GTGGTGTGTCGGCATGCAC
4534	TGCATGCCGACACACCACT	AGTGGTGTGTCGGCATGCA
4535	GCATGCCGACACACCACTG	CAGTGGTGTGTCGGCATGC
4536	CATGCCGACACACCACTGC	GCAGTGGTGTGTCGGCATG
4537	ATGCCGACACACCACTGCC	GGCAGTGGTGTGTCGGCAT
4538	TGCCGACACACCACTGCCT	AGGCAGTGGTGTGTCGGCA
4539	GCCGACACACCACTGCCTG	CAGGCAGTGGTGTGTCGGC
4540	CCGACACACCACTGCCTGC	GCAGGCAGTGGTGTGTCGG
4541	CGACACACCACTGCCTGCC	GGCAGGCAGTGGTGTGTCG
4542	GACACACCACTGCCTGCCT	AGGCAGGCAGTGGTGTGTC
4543	ACACACCACTGCCTGCCTG	CAGGCAGGCAGTGGTGTGT
4544	CACACCACTGCCTGCCTGG	CCAGGCAGGCAGTGGTGTG
4545	ACACCACTGCCTGCCTGGC	GCCAGGCAGGCAGTGGTGT
4546	CACCACTGCCTGCCTGGCA	TGCCAGGCAGGCAGTGGTG
4547	ACCACTGCCTGCCTGGCAC	GTGCCAGGCAGGCAGTGGT
4548	CCACTGCCTGCCTGGCACC	GGTGCCAGGCAGGCAGTGG
4549	CACTGCCTGCCTGGCACCG	CGGTGCCAGGCAGGCAGTG
4550	ACTGCCTGCCTGGCACCGG	CCGGTGCCAGGCAGGCAGT
4551	CTGCCTGCCTGGCACCGGG	CCCGGTGCCAGGCAGGCAG
4552	TGCCTGCCTGGCACCGGGC	GCCCGGTGCCAGGCAGGCA
4553	GCCTGCCTGGCACCGGGCA	TGCCCGGTGCCAGGCAGGC
4554	CCTGCCTGGCACCGGGCAC	GTGCCCGGTGCCAGGCAGG
4555	CTGCCTGGCACCGGGCACA	TGTGCCCGGTGCCAGGCAG
4556	TGCCTGGCACCGGGCACAG	CTGTGCCCGGTGCCAGGCA
4557	GCCTGGCACCGGGCACAGA	TCTGTGCCCGGTGCCAGGC
4558	CCTGGCACCGGGCACAGAA	TTCTGTGCCCGGTGCCAGG
4559	CTGGCACCGGGCACAGAAA	TTTCTGTGCCCGGTGCCAG
4560	TGGCACCGGGCACAGAAAG	CTTTCTGTGCCCGGTGCCA
4561	GGCACCGGGCACAGAAAGA	TCTTTCTGTGCCCGGTGCC
4562	GCACCGGGCACAGAAAGAC	GTCTTTCTGTGCCCGGTGC
4563	CACCGGGCACAGAAAGACT	AGTCTTTCTGTGCCCGGTG
4564	ACCGGGCACAGAAAGACTT	AAGTCTTTCTGTGCCCGGT
4565	CCGGGCACAGAAAGACTTC	GAAGTCTTTCTGTGCCCGG
4566	CGGGCACAGAAAGACTTCC	GGAAGTCTTTCTGTGCCCG
4567	GGGCACAGAAAGACTTCCT	AGGAAGTCTTTCTGTGCCC
4568	GGCACAGAAAGACTTCCTT	AAGGAAGTCTTTCTGTGCC
4569	GCACAGAAAGACTTCCTTT	AAAGGAAGTCTTTCTGTGC
4570	CACAGAAAGACTTCCTTTC	GAAAGGAAGTCTTTCTGTG
4571	ACAGAAAGACTTCCTTTCA	TGAAAGGAAGTCTTTCTGT
4572	CAGAAAGACTTCCTTTCAG	CTGAAAGGAAGTCTTTCTG
4573	AGAAAGACTTCCTTTCAGG	CCTGAAAGGAAGTCTTTCT
4574	GAAAGACTTCCTTTCAGGC	GCCTGAAAGGAAGTCTTTC
4575	AAAGACTTCCTTTCAGGCC	GGCCTGAAAGGAAGTCTTT
4576	AAGACTTCCTTTCAGGCCT	AGGCCTGAAAGGAAGTCTT
4577	AGACTTCCTTTCAGGCCTG	CAGGCCTGAAAGGAAGTCT
4578	GACTTCCTTTCAGGCCTGG	CCAGGCCTGAAAGGAAGTC
4579	ACTTCCTTTCAGGCCTGGA	TCCAGGCCTGAAAGGAAGT
4580	CTTCCTTTCAGGCCTGGAC	GTCCAGGCCTGAAAGGAAG
4581	TTCCTTTCAGGCCTGGACG	CGTCCAGGCCTGAAAGGAA
4582	TCCTTTCAGGCCTGGACGG	CCGTCCAGGCCTGAAAGGA
4583	CCTTTCAGGCCTGGACGGG	CCCGTCCAGGCCTGAAAGG
4584	CTTTCAGGCCTGGACGGGG	CCCCGTCCAGGCCTGAAAG
4585	TTTCAGGCCTGGACGGGGA	TCCCCGTCCAGGCCTGAAA
4586	TTCAGGCCTGGACGGGGAG	CTCCCCGTCCAGGCCTGAA
4587	TCAGGCCTGGACGGGGAGG	CCTCCCCGTCCAGGCCTGA
4588	CAGGCCTGGACGGGGAGGG	CCCTCCCCGTCCAGGCCTG
4589	AGGCCTGGACGGGGAGGGG	CCCCTCCCCGTCCAGGCCT
4590	GGCCTGGACGGGGAGGGGC	GCCCCTCCCCGTCCAGGCC
4591	GCCTGGACGGGGAGGGGCT	AGCCCCTCCCCGTCCAGGC
4592	CCTGGACGGGGAGGGGCTC	GAGCCCCTCCCCGTCCAGG
4593	CTGGACGGGGAGGGGCTCT	AGAGCCCCTCCCCGTCCAG
4594	TGGACGGGGAGGGGCTCTG	CAGAGCCCCTCCCCGTCCA
4595	GGACGGGGAGGGGCTCTGG	CCAGAGCCCCTCCCCGTCC
4596	GACGGGGAGGGGCTCTGGT	ACCAGAGCCCCTCCCCGTC
4597	ACGGGGAGGGGCTCTGGTC	GACCAGAGCCCCTCCCCGT
4598	CGGGGAGGGGCTCTGGTCT	AGACCAGAGCCCCTCCCCG
4599	GGGGAGGGGCTCTGGTCTC	GAGACCAGAGCCCCTCCCC
4600	GGGAGGGGCTCTGGTCTCC	GGAGACCAGAGCCCCTCCC
4601	GGAGGGGCTCTGGTCTCCG	CGGAGACCAGAGCCCCTCC
4602	GAGGGGCTCTGGTCTCCGG	CCGGAGACCAGAGCCCCTC
4603	AGGGGCTCTGGTCTCCGGG	CCCGGAGACCAGAGCCCCT
4604	GGGGCTCTGGTCTCCGGGC	GCCCGGAGACCAGAGCCCC
4605	GGGCTCTGGTCTCCGGGCA	TGCCCGGAGACCAGAGCCC
4606	GGCTCTGGTCTCCGGGCAG	CTGCCCGGAGACCAGAGCC
4607	GCTCTGGTCTCCGGGCAGC	GCTGCCCGGAGACCAGAGC
4608	CTCTGGTCTCCGGGCAGCC	GGCTGCCCGGAGACCAGAG
4609	TCTGGTCTCCGGGCAGCCA	TGGCTGCCCGGAGACCAGA
4610	CTGGTCTCCGGGCAGCCAG	CTGGCTGCCCGGAGACCAG
4611	TGGTCTCCGGGCAGCCAGG	CCTGGCTGCCCGGAGACCA
4612	GGTCTCCGGGCAGCCAGGT	ACCTGGCTGCCCGGAGACC
4613	GTCTCCGGGCAGCCAGGTC	GACCTGGCTGCCCGGAGAC
4614	TCTCCGGGCAGCCAGGTCA	TGACCTGGCTGCCCGGAGA
4615	CTCCGGGCAGCCAGGTCAG	CTGACCTGGCTGCCCGGAG
4616	TCCGGGCAGCCAGGTCAGC	GCTGACCTGGCTGCCCGGA
4617	CCGGGCAGCCAGGTCAGCA	TGCTGACCTGGCTGCCCGG
4618	CGGGCAGCCAGGTCAGCAC	GTGCTGACCTGGCTGCCCG
4619	GGGCAGCCAGGTCAGCACT	AGTGCTGACCTGGCTGCCC
4620	GGCAGCCAGGTCAGCACTG	CAGTGCTGACCTGGCTGCC
4621	GCAGCCAGGTCAGCACTGT	ACAGTGCTGACCTGGCTGC
4622	CAGCCAGGTCAGCACTGTG	CACAGTGCTGACCTGGCTG
4623	AGCCAGGTCAGCACTGTGT	ACACAGTGCTGACCTGGCT
4624	GCCAGGTCAGCACTGTGTG	CACACAGTGCTGACCTGGC
4625	CCAGGTCAGCACTGTGTGG	CCACACAGTGCTGACCTGG
4626	CAGGTCAGCACTGTGTGGC	GCCACACAGTGCTGACCTG
4627	AGGTCAGCACTGTGTGGCA	TGCCACACAGTGCTGACCT
4628	GGTCAGCACTGTGTGGCAC	GTGCCACACAGTGCTGACC
4629	GTCAGCACTGTGTGGCACG	CGTGCCACACAGTGCTGAC
4630	TCAGCACTGTGTGGCACGT	ACGTGCCACACAGTGCTGA
4631	CAGCACTGTGTGGCACGTG	CACGTGCCACACAGTGCTG
4632	AGCACTGTGTGGCACGTGT	ACACGTGCCACACAGTGCT
4633	GCACTGTGTGGCACGTGTT	AACACGTGCCACACAGTGC
4634	CACTGTGTGGCACGTGTTC	GAACACGTGCCACACAGTG
4635	ACTGTGTGGCACGTGTTCC	GGAACACGTGCCACACAGT
4636	CTGTGTGGCACGTGTTCCG	CGGAACACGTGCCACACAG
4637	TGTGTGGCACGTGTTCCGG	CCGGAACACGTGCCACACA
4638	GTGTGGCACGTGTTCCGGG	CCCGGAACACGTGCCACAC
4639	TGTGGCACGTGTTCCGGGC	GCCCGGAACACGTGCCACA
4640	GTGGCACGTGTTCCGGGCA	TGCCCGGAACACGTGCCAC
4641	TGGCACGTGTTCCGGGCAC	GTGCCCGGAACACGTGCCA
4642	GGCACGTGTTCCGGGCACA	TGTGCCCGGAACACGTGCC
4643	GCACGTGTTCCGGGCACAG	CTGTGCCCGGAACACGTGC
4644	CACGTGTTCCGGGCACAGG	CCTGTGCCCGGAACACGTG
4645	ACGTGTTCCGGGCACAGGA	TCCTGTGCCCGGAACACGT
4646	CGTGTTCCGGGCACAGGAC	GTCCTGTGCCCGGAACACG
4647	GTGTTCCGGGCACAGGACG	CGTCCTGTGCCCGGAACAC
4648	TGTTCCGGGCACAGGACGC	GCGTCCTGTGCCCGGAACA
4649	GTTCCGGGCACAGGACGCC	GGCGTCCTGTGCCCGGAAC
4650	TTCCGGGCACAGGACGCCC	GGGCGTCCTGTGCCCGGAA
4651	TCCGGGCACAGGACGCCCA	TGGGCGTCCTGTGCCCGGA
4652	CCGGGCACAGGACGCCCAG	CTGGGCGTCCTGTGCCCGG
4653	CGGGCACAGGACGCCCAGC	GCTGGGCGTCCTGTGCCCG
4654	GGGCACAGGACGCCCAGCG	CGCTGGGCGTCCTGTGCCC
4655	GGCACAGGACGCCCAGCGC	GCGCTGGGCGTCCTGTGCC
4656	GCACAGGACGCCCAGCGCA	TGCGCTGGGCGTCCTGTGC
4657	CACAGGACGCCCAGCGCAT	ATGCGCTGGGCGTCCTGTG
4658	ACAGGACGCCCAGCGCATC	GATGCGCTGGGCGTCCTGT
4659	CAGGACGCCCAGCGCATCC	GGATGCGCTGGGCGTCCTG
4660	AGGACGCCCAGCGCATCCG	CGGATGCGCTGGGCGTCCT
4661	GGACGCCCAGCGCATCCGC	GCGGATGCGCTGGGCGTCC
4662	GACGCCCAGCGCATCCGCC	GGCGGATGCGCTGGGCGTC
4663	ACGCCCAGCGCATCCGCCG	CGGCGGATGCGCTGGGCGT
4664	CGCCCAGCGCATCCGCCGC	GCGGCGGATGCGCTGGGCG
4665	GCCCAGCGCATCCGCCGCT	AGCGGCGGATGCGCTGGGC
4666	CCCAGCGCATCCGCCGCTT	AAGCGGCGGATGCGCTGGG
4667	CCAGCGCATCCGCCGCTTT	AAAGCGGCGGATGCGCTGG
4668	CAGCGCATCCGCCGCTTTC	GAAAGCGGCGGATGCGCTG
4669	AGCGCATCCGCCGCTTTCT	AGAAAGCGGCGGATGCGCT
4670	GCGCATCCGCCGCTTTCTC	GAGAAAGCGGCGGATGCGC
4671	CGCATCCGCCGCTTTCTCC	GGAGAAAGCGGCGGATGCG
4672	GCATCCGCCGCTTTCTCCA	TGGAGAAAGCGGCGGATGC
4673	CATCCGCCGCTTTCTCCAG	CTGGAGAAAGCGGCGGATG
4674	ATCCGCCGCTTTCTCCAGA	TCTGGAGAAAGCGGCGGAT
4675	TCCGCCGCTTTCTCCAGAT	ATCTGGAGAAAGCGGCGGA
4676	CCGCCGCTTTCTCCAGATG	CATCTGGAGAAAGCGGCGG
4677	CGCCGCTTTCTCCAGATGG	CCATCTGGAGAAAGCGGCG
4678	GCCGCTTTCTCCAGATGGT	ACCATCTGGAGAAAGCGGC
4679	CCGCTTTCTCCAGATGGTG	CACCATCTGGAGAAAGCGG
4680	CGCTTTCTCCAGATGGTGT	ACACCATCTGGAGAAAGCG
4681	GCTTTCTCCAGATGGTGTG	CACACCATCTGGAGAAAGC
4682	CTTTCTCCAGATGGTGTGC	GCACACCATCTGGAGAAAG
4683	TTTCTCCAGATGGTGTGCC	GGCACACCATCTGGAGAAA
4684	TTCTCCAGATGGTGTGCCC	GGGCACACCATCTGGAGAA
4685	TCTCCAGATGGTGTGCCCG	CGGGCACACCATCTGGAGA
4686	CTCCAGATGGTGTGCCCGG	CCGGGCACACCATCTGGAG
4687	TCCAGATGGTGTGCCCGGC	GCCGGGCACACCATCTGGA
4688	CCAGATGGTGTGCCCGGCC	GGCCGGGCACACCATCTGG
4689	CAGATGGTGTGCCCGGCCG	CGGCCGGGCACACCATCTG
4690	AGATGGTGTGCCCGGCCGG	CCGGCCGGGCACACCATCT
4691	GATGGTGTGCCCGGCCGGG	CCCGGCCGGGCACACCATC
4692	ATGGTGTGCCCGGCCGGGG	CCCCGGCCGGGCACACCAT
4693	TGGTGTGCCCGGCCGGGGC	GCCCCGGCCGGGCACACCA
4694	GGTGTGCCCGGCCGGGGCA	TGCCCCGGCCGGGCACACC
4695	GTGTGCCCGGCCGGGGCAG	CTGCCCCGGCCGGGCACAC
4696	TGTGCCCGGCCGGGGCAGG	CCTGCCCCGGCCGGGCACA
4697	GTGCCCGGCCGGGGCAGGC	GCCTGCCCCGGCCGGGCAC
4698	TGCCCGGCCGGGGCAGGCG	CGCCTGCCCCGGCCGGGCA
4699	GCCCGGCCGGGGCAGGCGC	GCGCCTGCCCCGGCCGGGC
4700	CCCGGCCGGGGCAGGCGCC	GGCGCCTGCCCCGGCCGGG
4701	CCGGCCGGGGCAGGCGCCC	GGGCGCCTGCCCCGGCCGG
4702	CGGCCGGGGCAGGCGCCCT	AGGGCGCCTGCCCCGGCCG
4703	GGCCGGGGCAGGCGCCCTG	CAGGGCGCCTGCCCCGGCC
4704	GCCGGGGCAGGCGCCCTGG	CCAGGGCGCCTGCCCCGGC
4705	CCGGGGCAGGCGCCCTGGA	TCCAGGGCGCCTGCCCCGG
4706	CGGGGCAGGCGCCCTGGAG	CTCCAGGGCGCCTGCCCCG
4707	GGGGCAGGCGCCCTGGAGC	GCTCCAGGGCGCCTGCCCC
4708	GGGCAGGCGCCCTGGAGCC	GGCTCCAGGGCGCCTGCCC
4709	GGCAGGCGCCCTGGAGCCT	AGGCTCCAGGGCGCCTGCC
4710	GCAGGCGCCCTGGAGCCTG	CAGGCTCCAGGGCGCCTGC
4711	CAGGCGCCCTGGAGCCTGG	CCAGGCTCCAGGGCGCCTG
4712	AGGCGCCCTGGAGCCTGGC	GCCAGGCTCCAGGGCGCCT
4713	GGCGCCCTGGAGCCTGGCG	CGCCAGGCTCCAGGGCGCC
4714	GCGCCCTGGAGCCTGGCGC	GCGCCAGGCTCCAGGGCGC
4715	CGCCCTGGAGCCTGGCGCC	GGCGCCAGGCTCCAGGGCG
4716	GCCCTGGAGCCTGGCGCCC	GGGCGCCAGGCTCCAGGGC
4717	CCCTGGAGCCTGGCGCCCC	GGGGCGCCAGGCTCCAGGG
4718	CCTGGAGCCTGGCGCCCCA	TGGGGCGCCAGGCTCCAGG
4719	CTGGAGCCTGGCGCCCCAG	CTGGGGCGCCAGGCTCCAG
4720	TGGAGCCTGGCGCCCCAGG	CCTGGGGCGCCAGGCTCCA
4721	GGAGCCTGGCGCCCCAGGC	GCCTGGGGCGCCAGGCTCC
4722	GAGCCTGGCGCCCCAGGCA	TGCCTGGGGCGCCAGGCTC
4723	AGCCTGGCGCCCCAGGCAG	CTGCCTGGGGCGCCAGGCT
4724	GCCTGGCGCCCCAGGCAGC	GCTGCCTGGGGCGCCAGGC
4725	CCTGGCGCCCCAGGCAGCT	AGCTGCCTGGGGCGCCAGG
4726	CTGGCGCCCCAGGCAGCTG	CAGCTGCCTGGGGCGCCAG
4727	TGGCGCCCCAGGCAGCTGC	GCAGCTGCCTGGGGCGCCA
4728	GGCGCCCCAGGCAGCTGCT	AGCAGCTGCCTGGGGCGCC
4729	GCGCCCCAGGCAGCTGCTA	TAGCAGCTGCCTGGGGCGC
4730	CGCCCCAGGCAGCTGCTAC	GTAGCAGCTGCCTGGGGCG
4731	GCCCCAGGCAGCTGCTACC	GGTAGCAGCTGCCTGGGGC
4732	CCCCAGGCAGCTGCTACCT	AGGTAGCAGCTGCCTGGGG
4733	CCCAGGCAGCTGCTACCTG	CAGGTAGCAGCTGCCTGGG
4734	CCAGGCAGCTGCTACCTGG	CCAGGTAGCAGCTGCCTGG
4735	CAGGCAGCTGCTACCTGGA	TCCAGGTAGCAGCTGCCTG
4736	AGGCAGCTGCTACCTGGAT	ATCCAGGTAGCAGCTGCCT
4737	GGCAGCTGCTACCTGGATG	CATCCAGGTAGCAGCTGCC
4738	GCAGCTGCTACCTGGATGC	GCATCCAGGTAGCAGCTGC
4739	CAGCTGCTACCTGGATGCA	TGCATCCAGGTAGCAGCTG
4740	AGCTGCTACCTGGATGCAG	CTGCATCCAGGTAGCAGCT
4741	GCTGCTACCTGGATGCAGG	CCTGCATCCAGGTAGCAGC
4742	CTGCTACCTGGATGCAGGG	CCCTGCATCCAGGTAGCAG
4743	TGCTACCTGGATGCAGGGC	GCCCTGCATCCAGGTAGCA
4744	GCTACCTGGATGCAGGGCT	AGCCCTGCATCCAGGTAGC
4745	CTACCTGGATGCAGGGCTG	CAGCCCTGCATCCAGGTAG
4746	TACCTGGATGCAGGGCTGC	GCAGCCCTGCATCCAGGTA
4747	ACCTGGATGCAGGGCTGCG	CGCAGCCCTGCATCCAGGT
4748	CCTGGATGCAGGGCTGCGG	CCGCAGCCCTGCATCCAGG
4749	CTGGATGCAGGGCTGCGGC	GCCGCAGCCCTGCATCCAG
4750	TGGATGCAGGGCTGCGGCG	CGCCGCAGCCCTGCATCCA
4751	GGATGCAGGGCTGCGGCGG	CCGCCGCAGCCCTGCATCC
4752	GATGCAGGGCTGCGGCGGC	GCCGCCGCAGCCCTGCATC
4753	ATGCAGGGCTGCGGCGGCG	CGCCGCCGCAGCCCTGCAT
4754	TGCAGGGCTGCGGCGGCGC	GCGCCGCCGCAGCCCTGCA
4755	GCAGGGCTGCGGCGGCGCC	GGCGCCGCCGCAGCCCTGC
4756	CAGGGCTGCGGCGGCGCCT	AGGCGCCGCCGCAGCCCTG
4757	AGGGCTGCGGCGGCGCCTG	CAGGCGCCGCCGCAGCCCT
4758	GGGCTGCGGCGGCGCCTGC	GCAGGCGCCGCCGCAGCCC
4759	GGCTGCGGCGGCGCCTGCG	CGCAGGCGCCGCCGCAGCC
4760	GCTGCGGCGGCGCCTGCGG	CCGCAGGCGCCGCCGCAGC
4761	CTGCGGCGGCGCCTGCGGG	CCCGCAGGCGCCGCCGCAG
4762	TGCGGCGGCGCCTGCGGGA	TCCCGCAGGCGCCGCCGCA
4763	GCGGCGGCGCCTGCGGGAG	CTCCCGCAGGCGCCGCCGC
4764	CGGCGGCGCCTGCGGGAGG	CCTCCCGCAGGCGCCGCCG
4765	GGCGGCGCCTGCGGGAGGA	TCCTCCCGCAGGCGCCGCC
4766	GCGGCGCCTGCGGGAGGAG	CTCCTCCCGCAGGCGCCGC
4767	CGGCGCCTGCGGGAGGAGT	ACTCCTCCCGCAGGCGCCG
4768	GGCGCCTGCGGGAGGAGTG	CACTCCTCCCGCAGGCGCC
4769	GCGCCTGCGGGAGGAGTGG	CCACTCCTCCCGCAGGCGC
4770	CGCCTGCGGGAGGAGTGGG	CCCACTCCTCCCGCAGGCG
4771	GCCTGCGGGAGGAGTGGGG	CCCCACTCCTCCCGCAGGC
4772	CCTGCGGGAGGAGTGGGGC	GCCCCACTCCTCCCGCAGG
4773	CTGCGGGAGGAGTGGGGCG	CGCCCCACTCCTCCCGCAG
4774	TGCGGGAGGAGTGGGGCGT	ACGCCCCACTCCTCCCGCA
4775	GCGGGAGGAGTGGGGCGTG	CACGCCCCACTCCTCCCGC
4776	CGGGAGGAGTGGGGCGTGA	TCACGCCCCACTCCTCCCG
4777	GGGAGGAGTGGGGCGTGAG	CTCACGCCCCACTCCTCCC
4778	GGAGGAGTGGGGCGTGAGC	GCTCACGCCCCACTCCTCC
4779	GAGGAGTGGGGCGTGAGCT	AGCTCACGCCCCACTCCTC
4780	AGGAGTGGGGCGTGAGCTG	CAGCTCACGCCCCACTCCT
4781	GGAGTGGGGCGTGAGCTGC	GCAGCTCACGCCCCACTCC
4782	GAGTGGGGCGTGAGCTGCT	AGCAGCTCACGCCCCACTC
4783	AGTGGGGCGTGAGCTGCTG	CAGCAGCTCACGCCCCACT
4784	GTGGGGCGTGAGCTGCTGG	CCAGCAGCTCACGCCCCAC
4785	TGGGGCGTGAGCTGCTGGA	TCCAGCAGCTCACGCCCCA
4786	GGGGCGTGAGCTGCTGGAC	GTCCAGCAGCTCACGCCCC
4787	GGGCGTGAGCTGCTGGACC	GGTCCAGCAGCTCACGCCC
4788	GGCGTGAGCTGCTGGACCC	GGGTCCAGCAGCTCACGCC
4789	GCGTGAGCTGCTGGACCCT	AGGGTCCAGCAGCTCACGC
4790	CGTGAGCTGCTGGACCCTG	CAGGGTCCAGCAGCTCACG
4791	GTGAGCTGCTGGACCCTGC	GCAGGGTCCAGCAGCTCAC
4792	TGAGCTGCTGGACCCTGCT	AGCAGGGTCCAGCAGCTCA
4793	GAGCTGCTGGACCCTGCTC	GAGCAGGGTCCAGCAGCTC
4794	AGCTGCTGGACCCTGCTCC	GGAGCAGGGTCCAGCAGCT
4795	GCTGCTGGACCCTGCTCCA	TGGAGCAGGGTCCAGCAGC
4796	CTGCTGGACCCTGCTCCAG	CTGGAGCAGGGTCCAGCAG
4797	TGCTGGACCCTGCTCCAGG	CCTGGAGCAGGGTCCAGCA
4798	GCTGGACCCTGCTCCAGGC	GCCTGGAGCAGGGTCCAGC
4799	CTGGACCCTGCTCCAGGCC	GGCCTGGAGCAGGGTCCAG
4800	TGGACCCTGCTCCAGGCCC	GGGCCTGGAGCAGGGTCCA
4801	GGACCCTGCTCCAGGCCCC	GGGGCCTGGAGCAGGGTCC
4802	GACCCTGCTCCAGGCCCCC	GGGGGCCTGGAGCAGGGTC
4803	ACCCTGCTCCAGGCCCCCG	CGGGGGCCTGGAGCAGGGT
4804	CCCTGCTCCAGGCCCCCGG	CCGGGGGCCTGGAGCAGGG
4805	CCTGCTCCAGGCCCCCGGA	TCCGGGGGCCTGGAGCAGG
4806	CTGCTCCAGGCCCCCGGAG	CTCCGGGGGCCTGGAGCAG
4807	TGCTCCAGGCCCCCGGAGA	TCTCCGGGGGCCTGGAGCA
4808	GCTCCAGGCCCCCGGAGAG	CTCTCCGGGGGCCTGGAGC
4809	CTCCAGGCCCCCGGAGAGG	CCTCTCCGGGGGCCTGGAG
4810	TCCAGGCCCCCGGAGAGGC	GCCTCTCCGGGGGCCTGGA
4811	CCAGGCCCCCGGAGAGGCC	GGCCTCTCCGGGGGCCTGG
4812	CAGGCCCCCGGAGAGGCCG	CGGCCTCTCCGGGGGCCTG
4813	AGGCCCCCGGAGAGGCCGT	ACGGCCTCTCCGGGGGCCT
4814	GGCCCCCGGAGAGGCCGTG	CACGGCCTCTCCGGGGGCC
4815	GCCCCCGGAGAGGCCGTGC	GCACGGCCTCTCCGGGGGC
4816	CCCCCGGAGAGGCCGTGCT	AGCACGGCCTCTCCGGGGG
4817	CCCCGGAGAGGCCGTGCTG	CAGCACGGCCTCTCCGGGG
4818	CCCGGAGAGGCCGTGCTGG	CCAGCACGGCCTCTCCGGG
4819	CCGGAGAGGCCGTGCTGGT	ACCAGCACGGCCTCTCCGG
4820	CGGAGAGGCCGTGCTGGTG	CACCAGCACGGCCTCTCCG
4821	GGAGAGGCCGTGCTGGTGC	GCACCAGCACGGCCTCTCC
4822	GAGAGGCCGTGCTGGTGCC	GGCACCAGCACGGCCTCTC
4823	AGAGGCCGTGCTGGTGCCT	AGGCACCAGCACGGCCTCT
4824	GAGGCCGTGCTGGTGCCTG	CAGGCACCAGCACGGCCTC
4825	AGGCCGTGCTGGTGCCTGC	GCAGGCACCAGCACGGCCT
4826	GGCCGTGCTGGTGCCTGCA	TGCAGGCACCAGCACGGCC
4827	GCCGTGCTGGTGCCTGCAG	CTGCAGGCACCAGCACGGC
4828	CCGTGCTGGTGCCTGCAGG	CCTGCAGGCACCAGCACGG
4829	CGTGCTGGTGCCTGCAGGG	CCCTGCAGGCACCAGCACG
4830	GTGCTGGTGCCTGCAGGGG	CCCCTGCAGGCACCAGCAC
4831	TGCTGGTGCCTGCAGGGGC	GCCCCTGCAGGCACCAGCA
4832	GCTGGTGCCTGCAGGGGCT	AGCCCCTGCAGGCACCAGC
4833	CTGGTGCCTGCAGGGGCTC	GAGCCCCTGCAGGCACCAG
4834	TGGTGCCTGCAGGGGCTCC	GGAGCCCCTGCAGGCACCA
4835	GGTGCCTGCAGGGGCTCCC	GGGAGCCCCTGCAGGCACC
4836	GTGCCTGCAGGGGCTCCCC	GGGGAGCCCCTGCAGGCAC
4837	TGCCTGCAGGGGCTCCCCA	TGGGGAGCCCCTGCAGGCA
4838	GCCTGCAGGGGCTCCCCAC	GTGGGGAGCCCCTGCAGGC
4839	CCTGCAGGGGCTCCCCACC	GGTGGGGAGCCCCTGCAGG
4840	CTGCAGGGGCTCCCCACCA	TGGTGGGGAGCCCCTGCAG
4841	TGCAGGGGCTCCCCACCAG	CTGGTGGGGAGCCCCTGCA
4842	GCAGGGGCTCCCCACCAGG	CCTGGTGGGGAGCCCCTGC
4843	CAGGGGCTCCCCACCAGGT	ACCTGGTGGGGAGCCCCTG
4844	AGGGGCTCCCCACCAGGTG	CACCTGGTGGGGAGCCCCT
4845	GGGGCTCCCCACCAGGTGC	GCACCTGGTGGGGAGCCCC
4846	GGGCTCCCCACCAGGTGCA	TGCACCTGGTGGGGAGCCC
4847	GGCTCCCCACCAGGTGCAG	CTGCACCTGGTGGGGAGCC
4848	GCTCCCCACCAGGTGCAGG	CCTGCACCTGGTGGGGAGC
4849	CTCCCCACCAGGTGCAGGG	CCCTGCACCTGGTGGGGAG
4850	TCCCCACCAGGTGCAGGGC	GCCCTGCACCTGGTGGGGA
4851	CCCCACCAGGTGCAGGGCC	GGCCCTGCACCTGGTGGGG
4852	CCCACCAGGTGCAGGGCCT	AGGCCCTGCACCTGGTGGG
4853	CCACCAGGTGCAGGGCCTG	CAGGCCCTGCACCTGGTGG
4854	CACCAGGTGCAGGGCCTGG	CCAGGCCCTGCACCTGGTG
4855	ACCAGGTGCAGGGCCTGGT	ACCAGGCCCTGCACCTGGT
4856	CCAGGTGCAGGGCCTGGTG	CACCAGGCCCTGCACCTGG
4857	CAGGTGCAGGGCCTGGTGA	TCACCAGGCCCTGCACCTG
4858	AGGTGCAGGGCCTGGTGAG	CTCACCAGGCCCTGCACCT
4859	GGTGCAGGGCCTGGTGAGC	GCTCACCAGGCCCTGCACC
4860	GTGCAGGGCCTGGTGAGCA	TGCTCACCAGGCCCTGCAC
4861	TGCAGGGCCTGGTGAGCAC	GTGCTCACCAGGCCCTGCA
4862	GCAGGGCCTGGTGAGCACA	TGTGCTCACCAGGCCCTGC
4863	CAGGGCCTGGTGAGCACAG	CTGTGCTCACCAGGCCCTG
4864	AGGGCCTGGTGAGCACAGT	ACTGTGCTCACCAGGCCCT
4865	GGGCCTGGTGAGCACAGTC	GACTGTGCTCACCAGGCCC
4866	GGCCTGGTGAGCACAGTCA	TGACTGTGCTCACCAGGCC
4867	GCCTGGTGAGCACAGTCAG	CTGACTGTGCTCACCAGGC
4868	CCTGGTGAGCACAGTCAGC	GCTGACTGTGCTCACCAGG
4869	CTGGTGAGCACAGTCAGCG	CGCTGACTGTGCTCACCAG
4870	TGGTGAGCACAGTCAGCGT	ACGCTGACTGTGCTCACCA
4871	GGTGAGCACAGTCAGCGTC	GACGCTGACTGTGCTCACC
4872	GTGAGCACAGTCAGCGTCA	TGACGCTGACTGTGCTCAC
4873	TGAGCACAGTCAGCGTCAC	GTGACGCTGACTGTGCTCA
4874	GAGCACAGTCAGCGTCACT	AGTGACGCTGACTGTGCTC
4875	AGCACAGTCAGCGTCACTC	GAGTGACGCTGACTGTGCT
4876	GCACAGTCAGCGTCACTCA	TGAGTGACGCTGACTGTGC
4877	CACAGTCAGCGTCACTCAG	CTGAGTGACGCTGACTGTG
4878	ACAGTCAGCGTCACTCAGC	GCTGAGTGACGCTGACTGT
4879	CAGTCAGCGTCACTCAGCA	TGCTGAGTGACGCTGACTG
4880	AGTCAGCGTCACTCAGCAC	GTGCTGAGTGACGCTGACT
4881	GTCAGCGTCACTCAGCACT	AGTGCTGAGTGACGCTGAC
4882	TCAGCGTCACTCAGCACTT	AAGTGCTGAGTGACGCTGA
4883	CAGCGTCACTCAGCACTTC	GAAGTGCTGAGTGACGCTG
4884	AGCGTCACTCAGCACTTCC	GGAAGTGCTGAGTGACGCT
4885	GCGTCACTCAGCACTTCCT	AGGAAGTGCTGAGTGACGC
4886	CGTCACTCAGCACTTCCTC	GAGGAAGTGCTGAGTGACG
4887	GTCACTCAGCACTTCCTCT	AGAGGAAGTGCTGAGTGAC
4888	TCACTCAGCACTTCCTCTC	GAGAGGAAGTGCTGAGTGA
4889	CACTCAGCACTTCCTCTCC	GGAGAGGAAGTGCTGAGTG
4890	ACTCAGCACTTCCTCTCCC	GGGAGAGGAAGTGCTGAGT
4891	CTCAGCACTTCCTCTCCCC	GGGGAGAGGAAGTGCTGAG
4892	TCAGCACTTCCTCTCCCCT	AGGGGAGAGGAAGTGCTGA
4893	CAGCACTTCCTCTCCCCTG	CAGGGGAGAGGAAGTGCTG
4894	AGCACTTCCTCTCCCCTGA	TCAGGGGAGAGGAAGTGCT
4895	GCACTTCCTCTCCCCTGAG	CTCAGGGGAGAGGAAGTGC
4896	CACTTCCTCTCCCCTGAGA	TCTCAGGGGAGAGGAAGTG
4897	ACTTCCTCTCCCCTGAGAC	GTCTCAGGGGAGAGGAAGT
4898	CTTCCTCTCCCCTGAGACC	GGTCTCAGGGGAGAGGAAG
4899	TTCCTCTCCCCTGAGACCT	AGGTCTCAGGGGAGAGGAA
4900	TCCTCTCCCCTGAGACCTC	GAGGTCTCAGGGGAGAGGA
4901	CCTCTCCCCTGAGACCTCT	AGAGGTCTCAGGGGAGAGG
4902	CTCTCCCCTGAGACCTCTG	CAGAGGTCTCAGGGGAGAG
4903	TCTCCCCTGAGACCTCTGC	GCAGAGGTCTCAGGGGAGA
4904	CTCCCCTGAGACCTCTGCC	GGCAGAGGTCTCAGGGGAG
4905	TCCCCTGAGACCTCTGCCC	GGGCAGAGGTCTCAGGGGA
4906	CCCCTGAGACCTCTGCCCT	AGGGCAGAGGTCTCAGGGG
4907	CCCTGAGACCTCTGCCCTC	GAGGGCAGAGGTCTCAGGG
4908	CCTGAGACCTCTGCCCTCT	AGAGGGCAGAGGTCTCAGG
4909	CTGAGACCTCTGCCCTCTC	GAGAGGGCAGAGGTCTCAG
4910	TGAGACCTCTGCCCTCTCT	AGAGAGGGCAGAGGTCTCA
4911	GAGACCTCTGCCCTCTCTG	CAGAGAGGGCAGAGGTCTC
4912	AGACCTCTGCCCTCTCTGC	GCAGAGAGGGCAGAGGTCT
4913	GACCTCTGCCCTCTCTGCT	AGCAGAGAGGGCAGAGGTC
4914	ACCTCTGCCCTCTCTGCTC	GAGCAGAGAGGGCAGAGGT
4915	CCTCTGCCCTCTCTGCTCA	TGAGCAGAGAGGGCAGAGG
4916	CTCTGCCCTCTCTGCTCAG	CTGAGCAGAGAGGGCAGAG
4917	TCTGCCCTCTCTGCTCAGC	GCTGAGCAGAGAGGGCAGA
4918	CTGCCCTCTCTGCTCAGCT	AGCTGAGCAGAGAGGGCAG
4919	TGCCCTCTCTGCTCAGCTC	GAGCTGAGCAGAGAGGGCA
4920	GCCCTCTCTGCTCAGCTCT	AGAGCTGAGCAGAGAGGGC
4921	CCCTCTCTGCTCAGCTCTG	CAGAGCTGAGCAGAGAGGG
4922	CCTCTCTGCTCAGCTCTGC	GCAGAGCTGAGCAGAGAGG
4923	CTCTCTGCTCAGCTCTGCC	GGCAGAGCTGAGCAGAGAG
4924	TCTCTGCTCAGCTCTGCCA	TGGCAGAGCTGAGCAGAGA
4925	CTCTGCTCAGCTCTGCCAC	GTGGCAGAGCTGAGCAGAG
4926	TCTGCTCAGCTCTGCCACC	GGTGGCAGAGCTGAGCAGA
4927	CTGCTCAGCTCTGCCACCA	TGGTGGCAGAGCTGAGCAG
4928	TGCTCAGCTCTGCCACCAG	CTGGTGGCAGAGCTGAGCA
4929	GCTCAGCTCTGCCACCAGG	CCTGGTGGCAGAGCTGAGC
4930	CTCAGCTCTGCCACCAGGG	CCCTGGTGGCAGAGCTGAG
4931	TCAGCTCTGCCACCAGGGA	TCCCTGGTGGCAGAGCTGA
4932	CAGCTCTGCCACCAGGGAC	GTCCCTGGTGGCAGAGCTG
4933	AGCTCTGCCACCAGGGACC	GGTCCCTGGTGGCAGAGCT
4934	GCTCTGCCACCAGGGACCC	GGGTCCCTGGTGGCAGAGC
4935	CTCTGCCACCAGGGACCCA	TGGGTCCCTGGTGGCAGAG
4936	TCTGCCACCAGGGACCCAG	CTGGGTCCCTGGTGGCAGA
4937	CTGCCACCAGGGACCCAGC	GCTGGGTCCCTGGTGGCAG
4938	TGCCACCAGGGACCCAGCC	GGCTGGGTCCCTGGTGGCA
4939	GCCACCAGGGACCCAGCCT	AGGCTGGGTCCCTGGTGGC
4940	CCACCAGGGACCCAGCCTT	AAGGCTGGGTCCCTGGTGG
4941	CACCAGGGACCCAGCCTTC	GAAGGCTGGGTCCCTGGTG
4942	ACCAGGGACCCAGCCTTCC	GGAAGGCTGGGTCCCTGGT
4943	CCAGGGACCCAGCCTTCCC	GGGAAGGCTGGGTCCCTGG
4944	CAGGGACCCAGCCTTCCCC	GGGGAAGGCTGGGTCCCTG
4945	AGGGACCCAGCCTTCCCCC	GGGGGAAGGCTGGGTCCCT
4946	GGGACCCAGCCTTCCCCCT	AGGGGGAAGGCTGGGTCCC
4947	GGACCCAGCCTTCCCCCTG	CAGGGGGAAGGCTGGGTCC
4948	GACCCAGCCTTCCCCCTGA	TCAGGGGGAAGGCTGGGTC
4949	ACCCAGCCTTCCCCCTGAC	GTCAGGGGGAAGGCTGGGT
4950	CCCAGCCTTCCCCCTGACT	AGTCAGGGGGAAGGCTGGG
4951	CCAGCCTTCCCCCTGACTG	CAGTCAGGGGGAAGGCTGG
4952	CAGCCTTCCCCCTGACTGC	GCAGTCAGGGGGAAGGCTG
4953	AGCCTTCCCCCTGACTGCC	GGCAGTCAGGGGGAAGGCT
4954	GCCTTCCCCCTGACTGCCA	TGGCAGTCAGGGGGAAGGC
4955	CCTTCCCCCTGACTGCCAC	GTGGCAGTCAGGGGGAAGG
4956	CTTCCCCCTGACTGCCACC	GGTGGCAGTCAGGGGGAAG
4957	TTCCCCCTGACTGCCACCT	AGGTGGCAGTCAGGGGGAA
4958	TCCCCCTGACTGCCACCTG	CAGGTGGCAGTCAGGGGGA
4959	CCCCCTGACTGCCACCTGC	GCAGGTGGCAGTCAGGGGG
4960	CCCCTGACTGCCACCTGCT	AGCAGGTGGCAGTCAGGGG
4961	CCCTGACTGCCACCTGCTT	AAGCAGGTGGCAGTCAGGG
4962	CCTGACTGCCACCTGCTTT	AAAGCAGGTGGCAGTCAGG
4963	CTGACTGCCACCTGCTTTA	TAAAGCAGGTGGCAGTCAG
4964	TGACTGCCACCTGCTTTAT	ATAAAGCAGGTGGCAGTCA
4965	GACTGCCACCTGCTTTATG	CATAAAGCAGGTGGCAGTC
4966	ACTGCCACCTGCTTTATGC	GCATAAAGCAGGTGGCAGT
4967	CTGCCACCTGCTTTATGCC	GGCATAAAGCAGGTGGCAG
4968	TGCCACCTGCTTTATGCCC	GGGCATAAAGCAGGTGGCA
4969	GCCACCTGCTTTATGCCCA	TGGGCATAAAGCAGGTGGC
4970	CCACCTGCTTTATGCCCAG	CTGGGCATAAAGCAGGTGG
4971	CACCTGCTTTATGCCCAGA	TCTGGGCATAAAGCAGGTG
4972	ACCTGCTTTATGCCCAGAT	ATCTGGGCATAAAGCAGGT
4973	CCTGCTTTATGCCCAGATG	CATCTGGGCATAAAGCAGG
4974	CTGCTTTATGCCCAGATGG	CCATCTGGGCATAAAGCAG
4975	TGCTTTATGCCCAGATGGA	TCCATCTGGGCATAAAGCA
4976	GCTTTATGCCCAGATGGAC	GTCCATCTGGGCATAAAGC
4977	CTTTATGCCCAGATGGACT	AGTCCATCTGGGCATAAAG
4978	TTTATGCCCAGATGGACTG	CAGTCCATCTGGGCATAAA
4979	TTATGCCCAGATGGACTGG	CCAGTCCATCTGGGCATAA
4980	TATGCCCAGATGGACTGGG	CCCAGTCCATCTGGGCATA
4981	ATGCCCAGATGGACTGGGC	GCCCAGTCCATCTGGGCAT
4982	TGCCCAGATGGACTGGGCT	AGCCCAGTCCATCTGGGCA
4983	GCCCAGATGGACTGGGCTG	CAGCCCAGTCCATCTGGGC
4984	CCCAGATGGACTGGGCTGT	ACAGCCCAGTCCATCTGGG
4985	CCAGATGGACTGGGCTGTG	CACAGCCCAGTCCATCTGG
4986	CAGATGGACTGGGCTGTGT	ACACAGCCCAGTCCATCTG
4987	AGATGGACTGGGCTGTGTT	AACACAGCCCAGTCCATCT
4988	GATGGACTGGGCTGTGTTC	GAACACAGCCCAGTCCATC
4989	ATGGACTGGGCTGTGTTCC	GGAACACAGCCCAGTCCAT
4990	TGGACTGGGCTGTGTTCCA	TGGAACACAGCCCAGTCCA
4991	GGACTGGGCTGTGTTCCAA	TTGGAACACAGCCCAGTCC
4992	GACTGGGCTGTGTTCCAAG	CTTGGAACACAGCCCAGTC
4993	ACTGGGCTGTGTTCCAAGC	GCTTGGAACACAGCCCAGT
4994	CTGGGCTGTGTTCCAAGCA	TGCTTGGAACACAGCCCAG
4995	TGGGCTGTGTTCCAAGCAG	CTGCTTGGAACACAGCCCA
4996	GGGCTGTGTTCCAAGCAGT	ACTGCTTGGAACACAGCCC
4997	GGCTGTGTTCCAAGCAGTG	CACTGCTTGGAACACAGCC
4998	GCTGTGTTCCAAGCAGTGA	TCACTGCTTGGAACACAGC
4999	CTGTGTTCCAAGCAGTGAA	TTCACTGCTTGGAACACAG
5000	TGTGTTCCAAGCAGTGAAG	CTTCACTGCTTGGAACACA
5001	GTGTTCCAAGCAGTGAAGG	CCTTCACTGCTTGGAACAC
5002	TGTTCCAAGCAGTGAAGGT	ACCTTCACTGCTTGGAACA
5003	GTTCCAAGCAGTGAAGGTG	CACCTTCACTGCTTGGAAC
5004	TTCCAAGCAGTGAAGGTGG	CCACCTTCACTGCTTGGAA
5005	TCCAAGCAGTGAAGGTGGC	GCCACCTTCACTGCTTGGA
5006	CCAAGCAGTGAAGGTGGCC	GGCCACCTTCACTGCTTGG
5007	CAAGCAGTGAAGGTGGCCG	CGGCCACCTTCACTGCTTG
5008	AAGCAGTGAAGGTGGCCGT	ACGGCCACCTTCACTGCTT
5009	AGCAGTGAAGGTGGCCGTG	CACGGCCACCTTCACTGCT
5010	GCAGTGAAGGTGGCCGTGG	CCACGGCCACCTTCACTGC
5011	CAGTGAAGGTGGCCGTGGG	CCCACGGCCACCTTCACTG
5012	AGTGAAGGTGGCCGTGGGG	CCCCACGGCCACCTTCACT
5013	GTGAAGGTGGCCGTGGGGA	TCCCCACGGCCACCTTCAC
5014	TGAAGGTGGCCGTGGGGAC	GTCCCCACGGCCACCTTCA
5015	GAAGGTGGCCGTGGGGACA	TGTCCCCACGGCCACCTTC
5016	AAGGTGGCCGTGGGGACAT	ATGTCCCCACGGCCACCTT
5017	AGGTGGCCGTGGGGACATT	AATGTCCCCACGGCCACCT
5018	GGTGGCCGTGGGGACATTA	TAATGTCCCCACGGCCACC
5019	GTGGCCGTGGGGACATTAC	GTAATGTCCCCACGGCCAC
5020	TGGCCGTGGGGACATTACA	TGTAATGTCCCCACGGCCA
5021	GGCCGTGGGGACATTACAG	CTGTAATGTCCCCACGGCC
5022	GCCGTGGGGACATTACAGG	CCTGTAATGTCCCCACGGC
5023	CCGTGGGGACATTACAGGA	TCCTGTAATGTCCCCACGG
5024	CGTGGGGACATTACAGGAG	CTCCTGTAATGTCCCCACG
5025	GTGGGGACATTACAGGAGG	CCTCCTGTAATGTCCCCAC
5026	TGGGGACATTACAGGAGGC	GCCTCCTGTAATGTCCCCA
5027	GGGGACATTACAGGAGGCC	GGCCTCCTGTAATGTCCCC
5028	GGGACATTACAGGAGGCCA	TGGCCTCCTGTAATGTCCC
5029	GGACATTACAGGAGGCCAA	TTGGCCTCCTGTAATGTCC
5030	GACATTACAGGAGGCCAAA	TTTGGCCTCCTGTAATGTC
5031	ACATTACAGGAGGCCAAAT	ATTTGGCCTCCTGTAATGT
5032	CATTACAGGAGGCCAAATA	TATTTGGCCTCCTGTAATG
5033	ATTACAGGAGGCCAAATAG	CTATTTGGCCTCCTGTAAT
5034	TTACAGGAGGCCAAATAGA	TCTATTTGGCCTCCTGTAA
5035	TACAGGAGGCCAAATAGAG	CTCTATTTGGCCTCCTGTA
5036	ACAGGAGGCCAAATAGAGG	CCTCTATTTGGCCTCCTGT
5037	CAGGAGGCCAAATAGAGGG	CCCTCTATTTGGCCTCCTG
5038	AGGAGGCCAAATAGAGGGA	TCCCTCTATTTGGCCTCCT
5039	GGAGGCCAAATAGAGGGAT	ATCCCTCTATTTGGCCTCC
5040	GAGGCCAAATAGAGGGATG	CATCCCTCTATTTGGCCTC
5041	AGGCCAAATAGAGGGATGC	GCATCCCTCTATTTGGCCT
5042	GGCCAAATAGAGGGATGCT	AGCATCCCTCTATTTGGCC
5043	GCCAAATAGAGGGATGCTA	TAGCATCCCTCTATTTGGC
5044	CCAAATAGAGGGATGCTAG	CTAGCATCCCTCTATTTGG
5045	CAAATAGAGGGATGCTAGG	CCTAGCATCCCTCTATTTG
5046	AAATAGAGGGATGCTAGGT	ACCTAGCATCCCTCTATTT
5047	AATAGAGGGATGCTAGGTG	CACCTAGCATCCCTCTATT
5048	ATAGAGGGATGCTAGGTGT	ACACCTAGCATCCCTCTAT
5049	TAGAGGGATGCTAGGTGTC	GACACCTAGCATCCCTCTA
5050	AGAGGGATGCTAGGTGTCT	AGACACCTAGCATCCCTCT
5051	GAGGGATGCTAGGTGTCTG	CAGACACCTAGCATCCCTC
5052	AGGGATGCTAGGTGTCTGG	CCAGACACCTAGCATCCCT
5053	GGGATGCTAGGTGTCTGGG	CCCAGACACCTAGCATCCC
5054	GGATGCTAGGTGTCTGGGA	TCCCAGACACCTAGCATCC
5055	GATGCTAGGTGTCTGGGAT	ATCCCAGACACCTAGCATC
5056	ATGCTAGGTGTCTGGGATC	GATCCCAGACACCTAGCAT
5057	TGCTAGGTGTCTGGGATCG	CGATCCCAGACACCTAGCA
5058	GCTAGGTGTCTGGGATCGG	CCGATCCCAGACACCTAGC
5059	CTAGGTGTCTGGGATCGGG	CCCGATCCCAGACACCTAG
5060	TAGGTGTCTGGGATCGGGG	CCCCGATCCCAGACACCTA
5061	AGGTGTCTGGGATCGGGGT	ACCCCGATCCCAGACACCT
5062	GGTGTCTGGGATCGGGGTG	CACCCCGATCCCAGACACC
5063	GTGTCTGGGATCGGGGTGG	CCACCCCGATCCCAGACAC
5064	TGTCTGGGATCGGGGTGGG	CCCACCCCGATCCCAGACA
5065	GTCTGGGATCGGGGTGGGG	CCCCACCCCGATCCCAGAC
5066	TCTGGGATCGGGGTGGGGA	TCCCCACCCCGATCCCAGA
5067	CTGGGATCGGGGTGGGGAC	GTCCCCACCCCGATCCCAG
5068	TGGGATCGGGGTGGGGACA	TGTCCCCACCCCGATCCCA
5069	GGGATCGGGGTGGGGACAG	CTGTCCCCACCCCGATCCC
5070	GGATCGGGGTGGGGACAGG	CCTGTCCCCACCCCGATCC
5071	GATCGGGGTGGGGACAGGT	ACCTGTCCCCACCCCGATC
5072	ATCGGGGTGGGGACAGGTA	TACCTGTCCCCACCCCGAT
5073	TCGGGGTGGGGACAGGTAG	CTACCTGTCCCCACCCCGA
5074	CGGGGTGGGGACAGGTAGA	TCTACCTGTCCCCACCCCG
5075	GGGGTGGGGACAGGTAGAC	GTCTACCTGTCCCCACCCC
5076	GGGTGGGGACAGGTAGACC	GGTCTACCTGTCCCCACCC
5077	GGTGGGGACAGGTAGACCA	TGGTCTACCTGTCCCCACC
5078	GTGGGGACAGGTAGACCAG	CTGGTCTACCTGTCCCCAC
5079	TGGGGACAGGTAGACCAGG	CCTGGTCTACCTGTCCCCA
5080	GGGGACAGGTAGACCAGGT	ACCTGGTCTACCTGTCCCC
5081	GGGACAGGTAGACCAGGTG	CACCTGGTCTACCTGTCCC
5082	GGACAGGTAGACCAGGTGC	GCACCTGGTCTACCTGTCC
5083	GACAGGTAGACCAGGTGCT	AGCACCTGGTCTACCTGTC
5084	ACAGGTAGACCAGGTGCTC	GAGCACCTGGTCTACCTGT
5085	CAGGTAGACCAGGTGCTCA	TGAGCACCTGGTCTACCTG
5086	AGGTAGACCAGGTGCTCAG	CTGAGCACCTGGTCTACCT
5087	GGTAGACCAGGTGCTCAGC	GCTGAGCACCTGGTCTACC
5088	GTAGACCAGGTGCTCAGCC	GGCTGAGCACCTGGTCTAC
5089	TAGACCAGGTGCTCAGCCC	GGGCTGAGCACCTGGTCTA
5090	AGACCAGGTGCTCAGCCCA	TGGGCTGAGCACCTGGTCT
5091	GACCAGGTGCTCAGCCCAG	CTGGGCTGAGCACCTGGTC
5092	ACCAGGTGCTCAGCCCAGG	CCTGGGCTGAGCACCTGGT
5093	CCAGGTGCTCAGCCCAGGC	GCCTGGGCTGAGCACCTGG
5094	CAGGTGCTCAGCCCAGGCA	TGCCTGGGCTGAGCACCTG
5095	AGGTGCTCAGCCCAGGCAC	GTGCCTGGGCTGAGCACCT
5096	GGTGCTCAGCCCAGGCACA	TGTGCCTGGGCTGAGCACC
5097	GTGCTCAGCCCAGGCACAA	TTGTGCCTGGGCTGAGCAC
5098	TGCTCAGCCCAGGCACAAC	GTTGTGCCTGGGCTGAGCA
5099	GCTCAGCCCAGGCACAACT	AGTTGTGCCTGGGCTGAGC
5100	CTCAGCCCAGGCACAACTT	AAGTTGTGCCTGGGCTGAG
5101	TCAGCCCAGGCACAACTTC	GAAGTTGTGCCTGGGCTGA
5102	CAGCCCAGGCACAACTTCA	TGAAGTTGTGCCTGGGCTG
5103	AGCCCAGGCACAACTTCAG	CTGAAGTTGTGCCTGGGCT
5104	GCCCAGGCACAACTTCAGC	GCTGAAGTTGTGCCTGGGC
5105	CCCAGGCACAACTTCAGCA	TGCTGAAGTTGTGCCTGGG
5106	CCAGGCACAACTTCAGCAG	CTGCTGAAGTTGTGCCTGG
5107	CAGGCACAACTTCAGCAGG	CCTGCTGAAGTTGTGCCTG
5108	AGGCACAACTTCAGCAGGG	CCCTGCTGAAGTTGTGCCT
5109	GGCACAACTTCAGCAGGGG	CCCCTGCTGAAGTTGTGCC
5110	GCACAACTTCAGCAGGGGA	TCCCCTGCTGAAGTTGTGC
5111	GACAACTTCAGCAGGGGAT	ATCCCCTGCTGAAGTTGTG
5112	ACAACTTCAGCAGGGGATG	CATCCCCTGCTGAAGTTGT
5113	CAACTTCAGCAGGGGATGG	CCATCCCCTGCTGAAGTTG
5114	AACTTCAGCAGGGGATGGC	GCCATCCCCTGCTGAAGTT
5115	ACTTCAGCAGGGGATGGCG	CGCCATCCCCTGCTGAAGT
5116	CTTCAGCAGGGGATGGCGC	GCGCCATCCCCTGCTGAAG
5117	TTCAGCAGGGGATGGCGCT	AGCGCCATCCCCTGCTGAA
5118	TCAGCAGGGGATGGCGCTA	TAGCGCCATCCCCTGCTGA
5119	CAGCAGGGGATGGCGCTAG	CTAGCGCCATCCCCTGCTG
5120	AGCAGGGGATGGCGCTAGG	CCTAGCGCCATCCCCTGCT
5121	GCAGGGGATGGCGCTAGGG	CCCTAGCGCCATCCCCTGC
5122	CAGGGGATGGCGCTAGGGG	CCCCTAGCGCCATCCCCTG
5123	AGGGGATGGCGCTAGGGGA	TCCCCTAGCGCCATCCCCT
5124	GGGGATGGCGCTAGGGGAC	GTCCCCTAGCGCCATCCCC
5125	GGGATGGCGCTAGGGGACT	AGTCCCCTAGCGCCATCCC
5126	GGATGGCGCTAGGGGACTT	AAGTCCCCTAGCGCCATCC
5127	GATGGCGCTAGGGGACTTG	CAAGTCCCCTAGCGCCATC
5128	ATGGCGCTAGGGGACTTGG	CCAAGTCCCCTAGCGCCAT
5129	TGGCGCTAGGGGACTTGGG	CCCAAGTCCCCTAGCGCCA
5130	GGCGCTAGGGGACTTGGGG	CCCCAAGTCCCCTAGCGCC
5131	GCGCTAGGGGACTTGGGGA	TCCCCAAGTCCCCTAGCGC
5132	CGCTAGGGGACTTGGGGAT	ATCCCCAAGTCCCCTAGCG
5133	GCTAGGGGACTTGGGGATT	AATCCCCAAGTCCCCTAGC
5134	CTAGGGGACTTGGGGATTT	AAATCCCCAAGTCCCCTAG
5135	TAGGGGACTTGGGGATTTC	GAAATCCCCAAGTCCCCTA
5136	AGGGGACTTGGGGATTTCT	AGAAATCCCCAAGTCCCCT
5137	GGGGACTTGGGGATTTCTG	CAGAAATCCCCAAGTCCCC
5138	GGGACTTGGGGATTTCTGG	CCAGAAATCCCCAAGTCCC
5139	GGACTTGGGGATTTCTGGT	ACCAGAAATCCCCAAGTCC
5140	GACTTGGGGATTTCTGGTC	GACCAGAAATCCCCAAGTC
5141	ACTTGGGGATTTCTGGTCA	TGACCAGAAATCCCCAAGT
5142	CTTGGGGATTTCTGGTCAA	TTGACCAGAAATCCCCAAG
5143	TTGGGGATTTCTGGTCAAC	GTTGACCAGAAATCCCCAA
5144	TGGGGATTTCTGGTCAACC	GGTTGACCAGAAATCCCCA
5145	GGGGATTTCTGGTCAACCC	GGGTTGACCAGAAATCCCC
5146	GGGATTTCTGGTCAACCCC	GGGGTTGACCAGAAATCCC
5147	GGATTTCTGGTCAACCCCA	TGGGGTTGACCAGAAATCC
5148	GATTTCTGGTCAACCCCAC	GTGGGGTTGACCAGAAATC
5149	ATTTCTGGTCAACCCCACA	TGTGGGGTTGACCAGAAAT
5150	TTTCTGGTCAACCCCACAA	TTGTGGGGTTGACCAGAAA
5151	TTCTGGTCAACCCCACAAG	CTTGTGGGGTTGACCAGAA
5152	TCTGGTCAACCCCACAAGC	GCTTGTGGGGTTGACCAGA
5153	CTGGTCAACCCCACAAGCA	TGCTTGTGGGGTTGACCAG
5154	TGGTCAACCCCACAAGCAC	GTGCTTGTGGGGTTGACCA
5155	GGTCAACCCCACAAGCACC	GGTGCTTGTGGGGTTGACC
5156	GTCAACCCCACAAGCACCA	TGGTGCTTGTGGGGTTGAC
5157	TCAACCCCACAAGCACCAC	GTGGTGCTTGTGGGGTTGA
5158	CAACCCCACAAGCACCACT	AGTGGTGCTTGTGGGGTTG
5159	AACCCCACAAGCACCACTC	GAGTGGTGCTTGTGGGGTT
5160	ACCCCACAAGCACCACTCT	AGAGTGGTGCTTGTGGGGT
5161	CCCCACAAGCACCACTCTG	CAGAGTGGTGCTTGTGGGG
5162	CCCACAAGCACCACTCTGG	CCAGAGTGGTGCTTGTGGG
5163	CCACAAGCACCACTCTGGG	CCCAGAGTGGTGCTTGTGG
5164	CACAAGCACCACTCTGGGC	GCCCAGAGTGGTGCTTGTG
5165	ACAAGCACCACTCTGGGCA	TGCCCAGAGTGGTGCTTGT
5166	CAAGCACCACTCTGGGCAC	GTGCCCAGAGTGGTGCTTG
5167	AAGCACCACTCTGGGCACA	TGTGCCCAGAGTGGTGCTT
5168	AGCACCACTCTGGGCACAA	TTGTGCCCAGAGTGGTGCT
5169	GCACCACTCTGGGCACAAG	CTTGTGCCCAGAGTGGTGC
5170	CACCACTCTGGGCACAAGC	GCTTGTGCCCAGAGTGGTG
5171	ACCACTCTGGGCACAAGCA	TGCTTGTGCCCAGAGTGGT
5172	CCACTCTGGGCACAAGCAG	CTGCTTGTGCCCAGAGTGG
5173	CACTCTGGGCACAAGCAGG	CCTGCTTGTGCCCAGAGTG
5174	ACTCTGGGCACAAGCAGGG	CCCTGCTTGTGCCCAGAGT
5175	CTCTGGGCACAAGCAGGGC	GCCCTGCTTGTGCCCAGAG
5176	TCTGGGCACAAGCAGGGCA	TGCCCTGCTTGTGCCCAGA
5177	CTGGGCACAAGCAGGGCAC	GTGCCCTGCTTGTGCCCAG
5178	TGGGCACAAGCAGGGCACT	AGTGCCCTGCTTGTGCCCA
5179	GGGCACAAGCAGGGCACTC	GAGTGCCCTGCTTGTGCCC
5180	GGCACAAGCAGGGCACTCT	AGAGTGCCCTGCTTGTGCC
5181	GCACAAGCAGGGCACTCTG	CAGAGTGCCCTGCTTGTGC
5182	CACAAGCAGGGCACTCTGT	ACAGAGTGCCCTGCTTGTG
5183	ACAAGCAGGGCACTCTGTT	AACAGAGTGCCCTGCTTGT
5184	CAAGCAGGGCACTCTGTTC	GAACAGAGTGCCCTGCTTG
5185	AAGCAGGGCACTCTGTTCC	GGAACAGAGTGCCCTGCTT
5186	AGCAGGGCACTCTGTTCCC	GGGAACAGAGTGCCCTGCT
5187	GCAGGGCACTCTGTTCCCC	GGGGAACAGAGTGCCCTGC
5188	CAGGGCACTCTGTTCCCCT	AGGGGAACAGAGTGCCCTG
5189	AGGGCACTCTGTTCCCCTC	GAGGGGAACAGAGTGCCCT
5190	GGGCACTCTGTTCCCCTCC	GGAGGGGAACAGAGTGCCC
5191	GGCACTCTGTTCCCCTCCC	GGGAGGGGAACAGAGTGCC
5192	GCACTCTGTTCCCCTCCCC	GGGGAGGGGAACAGAGTGC
5193	CACTCTGTTCCCCTCCCCC	GGGGGAGGGGAACAGAGTG
5194	ACTCTGTTCCCCTCCCCCT	AGGGGGAGGGGAACAGAGT
5195	CTCTGTTCCCCTCCCCCTT	AAGGGGGAGGGGAACAGAG
5196	TCTGTTCCCCTCCCCCTTA	TAAGGGGGAGGGGAACAGA
5197	CTGTTCCCCTCCCCCTTAA	TTAAGGGGGAGGGGAACAG
5198	TGTTCCCCTCCCCCTTAAG	CTTAAGGGGGAGGGGAACA
5199	GTTCCCCTCCCCCTTAAGC	GCTTAAGGGGGAGGGGAAC
5200	TTCCCCTCCCCCTTAAGCC	GGCTTAAGGGGGAGGGGAA
5201	TCCCCTCCCCCTTAAGCCA	TGGCTTAAGGGGGAGGGGA
5202	CCCCTCCCCCTTAAGCCAA	TTGGCTTAAGGGGGAGGGG
5203	CCCTCCCCCTTAAGCCAAC	GTTGGCTTAAGGGGGAGGG
5204	CCTCCCCCTTAAGCCAACA	TGTTGGCTTAAGGGGGAGG
5205	CTCCCCCTTAAGCCAACAA	TTGTTGGCTTAAGGGGGAG
5206	TCCCCCTTAAGCCAACAAC	GTTGTTGGCTTAAGGGGGA
5207	CCCCCTTAAGCCAACAACC	GGTTGTTGGCTTAAGGGGG
5208	CCCCTTAAGCCAACAACCA	TGGTTGTTGGCTTAAGGGG
5209	CCCTTAAGCCAACAACCAC	GTGGTTGTTGGCTTAAGGG
5210	CCTTAAGCCAACAACCACA	TGTGGTTGTTGGCTTAAGG
5211	CTTAAGCCAACAACCACAG	CTGTGGTTGTTGGCTTAAG
5212	TTAAGCCAACAACCACAGT	ACTGTGGTTGTTGGCTTAA
5213	TAAGCCAACAACCACAGTG	CACTGTGGTTGTTGGCTTA
5214	AAGCCAACAACCACAGTGC	GCACTGTGGTTGTTGGCTT
5215	AGCCAACAACCACAGTGCC	GGCACTGTGGTTGTTGGCT
5216	GCCAACAACCACAGTGCCA	TGGCACTGTGGTTGTTGGC
5217	CCAACAACCACAGTGCCAC	GTGGCACTGTGGTTGTTGG
5218	CAACAACCACAGTGCCACC	GGTGGCACTGTGGTTGTTG
5219	AACAACCACAGTGCCACCA	TGGTGGCACTGTGGTTGTT
5220	ACAACCACAGTGCCACCAA	TTGGTGGCACTGTGGTTGT
5221	CAACCACAGTGCCACCAAG	CTTGGTGGCACTGTGGTTG
5222	AACCACAGTGCCACCAAGC	GCTTGGTGGCACTGTGGTT
5223	ACCACAGTGCCACCAAGCT	AGCTTGGTGGCACTGTGGT
5224	CCACAGTGCCACCAAGCTC	GAGCTTGGTGGCACTGTGG
5225	CACAGTGCCACCAAGCTCA	TGAGCTTGGTGGCACTGTG
5226	ACAGTGCCACCAAGCTCAC	GTGAGCTTGGTGGCACTGT
5227	CAGTGCCACCAAGCTCACA	TGTGAGCTTGGTGGCACTG
5228	AGTGCCACCAAGCTCACAC	GTGTGAGCTTGGTGGCACT
5229	GTGCCACCAAGCTCACACC	GGTGTGAGCTTGGTGGCAC
5230	TGCCACCAAGCTCACACCT	AGGTGTGAGCTTGGTGGCA
5231	GCCACCAAGCTCACACCTG	CAGGTGTGAGCTTGGTGGC
5232	CCACCAAGCTCACACCTGT	ACAGGTGTGAGCTTGGTGG
5233	CACCAAGCTCACACCTGTC	GACAGGTGTGAGCTTGGTG
5234	ACCAAGCTCACACCTGTCC	GGACAGGTGTGAGCTTGGT
5235	CCAAGCTCACACCTGTCCT	AGGACAGGTGTGAGCTTGG
5236	CAAGCTCACACCTGTCCTT	AAGGACAGGTGTGAGCTTG
5237	AAGCTCACACCTGTCCTTC	GAAGGACAGGTGTGAGCTT
5238	AGCTCACACCTGTCCTTCT	AGAAGGACAGGTGTGAGCT
5239	GCTCACACCTGTCCTTCTC	GAGAAGGACAGGTGTGAGC
5240	CTCACACCTGTCCTTCTCA	TGAGAAGGACAGGTGTGAG
5241	TCACACCTGTCCTTCTCAG	CTGAGAAGGACAGGTGTGA
5242	CACACCTGTCCTTCTCAGG	CCTGAGAAGGACAGGTGTG
5243	ACACCTGTCCTTCTCAGGC	GCCTGAGAAGGACAGGTGT
5244	CACCTGTCCTTCTCAGGCT	AGCCTGAGAAGGACAGGTG
5245	ACCTGTCCTTCTCAGGCTG	CAGCCTGAGAAGGACAGGT
5246	CCTGTCCTTCTCAGGCTGG	CCAGCCTGAGAAGGACAGG
5247	CTGTCCTTCTCAGGCTGGC	GCCAGCCTGAGAAGGACAG
5248	TGTCCTTCTCAGGCTGGCA	TGCCAGCCTGAGAAGGACA
5249	GTCCTTCTCAGGCTGGCAT	ATGCCAGCCTGAGAAGGAC
5250	TCCTTCTCAGGCTGGCATC	GATGCCAGCCTGAGAAGGA
5251	CCTTCTCAGGCTGGCATCT	AGATGCCAGCCTGAGAAGG
5252	CTTCTCAGGCTGGCATCTC	GAGATGCCAGCCTGAGAAG
5253	TTCTCAGGCTGGCATCTCC	GGAGATGCCAGCCTGAGAA
5254	TCTCAGGCTGGCATCTCCC	GGGAGATGCCAGCCTGAGA
5255	CTCAGGCTGGCATCTCCCC	GGGGAGATGCCAGCCTGAG
5256	TCAGGCTGGCATCTCCCCC	GGGGGAGATGCCAGCCTGA
5257	CAGGCTGGCATCTCCCCCA	TGGGGGAGATGCCAGCCTG
5258	AGGCTGGCATCTCCCCCAC	GTGGGGGAGATGCCAGCCT
5259	GGCTGGCATCTCCCCCACC	GGTGGGGGAGATGCCAGCC
5260	GCTGGCATCTCCCCCACCC	GGGTGGGGGAGATGCCAGC
5261	CTGGCATCTCCCCCACCCT	AGGGTGGGGGAGATGCCAG
5262	TGGCATCTCCCCCACCCTG	CAGGGTGGGGGAGATGCCA
5263	GGCATCTCCCCCACCCTGT	ACAGGGTGGGGGAGATGCC
5264	GCATCTCCCCCACCCTGTG	CACAGGGTGGGGGAGATGC
5265	CATCTCCCCCACCCTGTGC	GCACAGGGTGGGGGAGATG
5266	ATCTCCCCCACCCTGTGCC	GGCACAGGGTGGGGGAGAT
5267	TCTCCCCCACCCTGTGCCC	GGGCACAGGGTGGGGGAGA
5268	CTCCCCCACCCTGTGCCCC	GGGGCACAGGGTGGGGGAG
5269	TCCCCCACCCTGTGCCCCT	AGGGGCACAGGGTGGGGGA
5270	CCCCCACCCTGTGCCCCTT	AAGGGGCACAGGGTGGGGG
5271	CCCCACCCTGTGCCCCTTT	AAAGGGGCACAGGGTGGGG
5272	CCCACCCTGTGCCCCTTTT	AAAAGGGGCACAGGGTGGG
5273	CCACCCTGTGCCCCTTTTC	GAAAAGGGGCACAGGGTGG
5274	CACCCTGTGCCCCTTTTCA	TGAAAAGGGGCACAGGGTG
5275	ACCCTGTGCCCCTTTTCAT	ATGAAAAGGGGCACAGGGT
5276	CCCTGTGCCCCTTTTCATG	CATGAAAAGGGGCACAGGG
5277	CCTGTGCCCCTTTTCATGG	CCATGAAAAGGGGCACAGG
5278	CTGTGCCCCTTTTCATGGT	ACCATGAAAAGGGGCACAG
5279	TGTGCCCCTTTTCATGGTA	TACCATGAAAAGGGGCACA
5280	GTGCCCCTTTTCATGGTAC	GTACCATGAAAAGGGGCAC
5281	TGCCCCTTTTCATGGTACC	GGTACCATGAAAAGGGGCA
5282	GCCCCTTTTCATGGTACCA	TGGTACCATGAAAAGGGGC
5283	CCCCTTTTCATGGTACCAG	CTGGTACCATGAAAAGGGG
5284	CCCTTTTCATGGTACCAGG	CCTGGTACCATGAAAAGGG
5285	CCTTTTCATGGTACCAGGC	GCCTGGTACCATGAAAAGG
5286	CTTTTCATGGTACCAGGCC	GGCCTGGTACCATGAAAAG
5287	TTTTCATGGTACCAGGCCC	GGGCCTGGTACCATGAAAA
5288	TTTCATGGTACCAGGCCCG	CGGGCCTGGTACCATGAAA
5289	TTCATGGTACCAGGCCCGC	GCGGGCCTGGTACCATGAA
5290	TCATGGTACCAGGCCCGCA	TGCGGGCCTGGTACCATGA
5291	CATGGTACCAGGCCCGCAC	GTGCGGGCCTGGTACCATG
5292	ATGGTACCAGGCCCGCACT	AGTGCGGGCCTGGTACCAT
5293	TGGTACCAGGCCCGCACTG	CAGTGCGGGCCTGGTACCA
5294	GGTACCAGGCCCGCACTGG	CCAGTGCGGGCCTGGTACC
5295	GTACCAGGCCCGCACTGGG	CCCAGTGCGGGCCTGGTAC
5296	TACCAGGCCCGCACTGGGG	CCCCAGTGCGGGCCTGGTA
5297	ACCAGGCCCGCACTGGGGG	CCCCCAGTGCGGGCCTGGT
5298	CCAGGCCCGCACTGGGGGC	GCCCCCAGTGCGGGCCTGG
5299	CAGGCCCGCACTGGGGGCA	TGCCCCCAGTGCGGGCCTG
5300	AGGCCCGCACTGGGGGCAA	TTGCCCCCAGTGCGGGCCT
5301	GGCCCGCACTGGGGGCAAT	ATTGCCCCCAGTGCGGGCC
5302	GCCCGCACTGGGGGCAATT	AATTGCCCCCAGTGCGGGC
5303	CCCGCACTGGGGGCAATTG	CAATTGCCCCCAGTGCGGG
5304	CCGCACTGGGGGCAATTGA	TCAATTGCCCCCAGTGCGG
5305	CGCACTGGGGGCAATTGAC	GTCAATTGCCCCCAGTGCG
5306	GCACTGGGGGCAATTGACT	AGTCAATTGCCCCCAGTGC
5307	CACTGGGGGCAATTGACTT	AAGTCAATTGCCCCCAGTG
5308	ACTGGGGGCAATTGACTTC	GAAGTCAATTGCCCCCAGT
5309	CTGGGGGCAATTGACTTCC	GGAAGTCAATTGCCCCCAG
5310	TGGGGGCAATTGACTTCCT	AGGAAGTCAATTGCCCCCA
5311	GGGGGCAATTGACTTCCTC	GAGGAAGTCAATTGCCCCC
5312	GGGGCAATTGACTTCCTCC	GGAGGAAGTCAATTGCCCC
5313	GGGCAATTGACTTCCTCCA	TGGAGGAAGTCAATTGCCC
5314	GGCAATTGACTTCCTCCAA	TTGGAGGAAGTCAATTGCC
5315	GCAATTGACTTCCTCCAAT	ATTGGAGGAAGTCAATTGC
5316	CAATTGACTTCCTCCAATC	GATTGGAGGAAGTCAATTG
5317	AATTGACTTCCTCCAATCC	GGATTGGAGGAAGTCAATT
5318	ATTGACTTCCTCCAATCCC	GGGATTGGAGGAAGTCAAT
5319	TTGACTTCCTCCAATCCCC	GGGGATTGGAGGAAGTCAA
5320	TGACTTCCTCCAATCCCCA	TGGGGATTGGAGGAAGTCA
5321	GACTTCCTCCAATCCCCAC	GTGGGGATTGGAGGAAGTC
5322	ACTTCCTCCAATCCCCACT	AGTGGGGATTGGAGGAAGT
5323	CTTCCTCCAATCCCCACTC	GAGTGGGGATTGGAGGAAG
5324	TTCCTCCAATCCCCACTCC	GGAGTGGGGATTGGAGGAA
5325	TCCTCCAATCCCCACTCCT	AGGAGTGGGGATTGGAGGA
5326	CCTCCAATCCCCACTCCTC	GAGGAGTGGGGATTGGAGG
5327	CTCCAATCCCCACTCCTCC	GGAGGAGTGGGGATTGGAG
5328	TCCAATCCCCACTCCTCCG	CGGAGGAGTGGGGATTGGA
5329	CCAATCCCCACTCCTCCGA	TCGGAGGAGTGGGGATTGG
5330	CAATCCCCACTCCTCCGAG	CTCGGAGGAGTGGGGATTG
5331	AATCCCCACTCCTCCGAGA	TCTCGGAGGAGTGGGGATT
5332	ATCCCCACTCCTCCGAGAC	GTCTCGGAGGAGTGGGGAT
5333	TCCCCACTCCTCCGAGACC	GGTCTCGGAGGAGTGGGGA
5334	CCCCACTCCTCCGAGACCC	GGGTCTCGGAGGAGTGGGG
5335	CCCACTCCTCCGAGACCCA	TGGGTCTCGGAGGAGTGGG
5336	CCACTCCTCCGAGACCCAG	CTGGGTCTCGGAGGAGTGG
5337	CACTCCTCCGAGACCCAGG	CCTGGGTCTCGGAGGAGTG
5338	ACTCCTCCGAGACCCAGGA	TCCTGGGTCTCGGAGGAGT
5339	CTCCTCCGAGACCCAGGAG	CTCCTGGGTCTCGGAGGAG
5340	TCCTCCGAGACCCAGGAGA	TCTCCTGGGTCTCGGAGGA
5341	CCTCCGAGACCCAGGAGAC	GTCTCCTGGGTCTCGGAGG
5342	CTCCGAGACCCAGGAGACA	TGTCTCCTGGGTCTCGGAG
5343	TCCGAGACCCAGGAGACAA	TTGTCTCCTGGGTCTCGGA
5344	CCGAGACCCAGGAGACAAA	TTTGTCTCCTGGGTCTCGG
5345	CGAGACCCAGGAGACAAAC	GTTTGTCTCCTGGGTCTCG
5346	GAGACCCAGGAGACAAACA	TGTTTGTCTCCTGGGTCTC
5347	AGACCCAGGAGACAAACAG	CTGTTTGTCTCCTGGGTCT
5348	GACCCAGGAGACAAACAGC	GCTGTTTGTCTCCTGGGTC
5349	ACCCAGGAGACAAACAGCC	GGCTGTTTGTCTCCTGGGT
5350	CCCAGGAGACAAACAGCCC	GGGCTGTTTGTCTCCTGGG
5351	CCAGGAGACAAACAGCCCT	AGGGCTGTTTGTCTCCTGG
5352	CAGGAGACAAACAGCCCTT	AAGGGCTGTTTGTCTCCTG
5353	AGGAGACAAACAGCCCTTC	GAAGGGCTGTTTGTCTCCT
5354	GGAGACAAACAGCCCTTCC	GGAAGGGCTGTTTGTCTCC
5355	GAGACAAACAGCCCTTCCT	AGGAAGGGCTGTTTGTCTC
5356	AGACAAACAGCCCTTCCTT	AAGGAAGGGCTGTTTGTCT
5357	GACAAACAGCCCTTCCTTG	CAAGGAAGGGCTGTTTGTC
5358	ACAAACAGCCCTTCCTTGG	CCAAGGAAGGGCTGTTTGT
5359	CAAACAGCCCTTCCTTGGG	CCCAAGGAAGGGCTGTTTG
5360	AAACAGCCCTTCCTTGGGG	CCCCAAGGAAGGGCTGTTT
5361	AACAGCCCTTCCTTGGGGA	TCCCCAAGGAAGGGCTGTT
5362	ACAGCCCTTCCTTGGGGAA	TTCCCCAAGGAAGGGCTGT
5363	CAGCCCTTCCTTGGGGAAA	TTTCCCCAAGGAAGGGCTG
5364	AGCCCTTCCTTGGGGAAAC	GTTTCCCCAAGGAAGGGCT
5365	GCCCTTCCTTGGGGAAACT	AGTTTCCCCAAGGAAGGGC
5366	CCCTTCCTTGGGGAAACTT	AAGTTTCCCCAAGGAAGGG
5367	CCTTCCTTGGGGAAACTTG	CAAGTTTCCCCAAGGAAGG
5368	CTTCCTTGGGGAAACTTGG	CCAAGTTTCCCCAAGGAAG
5369	TTCCTTGGGGAAACTTGGG	CCCAAGTTTCCCCAAGGAA
5370	TCCTTGGGGAAACTTGGGA	TCCCAAGTTTCCCCAAGGA
5371	CCTTGGGGAAACTTGGGAA	TTCCCAAGTTTCCCCAAGG
5372	CTTGGGGAAACTTGGGAAT	ATTCCCAAGTTTCCCCAAG
5373	TTGGGGAAACTTGGGAATC	GATTCCCAAGTTTCCCCAA
5374	TGGGGAAACTTGGGAATCA	TGATTCCCAAGTTTCCCCA
5375	GGGGAAACTTGGGAATCAT	ATGATTCCCAAGTTTCCCC
5376	GGGAAACTTGGGAATCATT	AATGATTCCCAAGTTTCCC
5377	GGAAACTTGGGAATCATTC	GAATGATTCCCAAGTTTCC
5378	GAAACTTGGGAATCATTCT	AGAATGATTCCCAAGTTTC
5379	AAACTTGGGAATCATTCTG	CAGAATGATTCCCAAGTTT
5380	AACTTGGGAATCATTCTGG	CCAGAATGATTCCCAAGTT
5381	ACTTGGGAATCATTCTGGC	GCCAGAATGATTCCCAAGT
5382	CTTGGGAATCATTCTGGCT	AGCCAGAATGATTCCCAAG
5383	TTGGGAATCATTCTGGCTT	AAGCCAGAATGATTCCCAA
5384	TGGGAATCATTCTGGCTTA	TAAGCCAGAATGATTCCCA
5385	GGGAATCATTCTGGCTTAA	TTAAGCCAGAATGATTCCC
5386	GGAATCATTCTGGCTTAAA	TTTAAGCCAGAATGATTCC
5387	GAATCATTCTGGCTTAAAC	GTTTAAGCCAGAATGATTC
5388	AATCATTCTGGCTTAAACA	TGTTTAAGCCAGAATGATT
5389	ATCATTCTGGCTTAAACAA	TTGTTTAAGCCAGAATGAT
5390	TCATTCTGGCTTAAACAAC	GTTGTTTAAGCCAGAATGA
5391	CATTCTGGCTTAAACAACA	TGTTGTTTAAGCCAGAATG
5392	ATTCTGGCTTAAACAACAC	GTGTTGTTTAAGCCAGAAT
5393	TTCTGGCTTAAACAACACC	GGTGTTGTTTAAGCCAGAA
5394	TCTGGCTTAAACAACACCT	AGGTGTTGTTTAAGCCAGA
5395	CTGGCTTAAACAACACCTC	GAGGTGTTGTTTAAGCCAG
5396	TGGCTTAAACAACACCTCC	GGAGGTGTTGTTTAAGCCA
5397	GGCTTAAACAACACCTCCT	AGGAGGTGTTGTTTAAGCC
5398	GCTTAAACAACACCTCCTC	GAGGAGGTGTTGTTTAAGC
5399	CTTAAACAACACCTCCTCC	GGAGGAGGTGTTGTTTAAG
5400	TTAAACAACACCTCCTCCT	AGGAGGAGGTGTTGTTTAA
5401	TAAACAACACCTCCTCCTG	CAGGAGGAGGTGTTGTTTA
5402	AAACAACACCTCCTCCTGC	GCAGGAGGAGGTGTTGTTT
5403	AACAACACCTCCTCCTGCT	AGCAGGAGGAGGTGTTGTT
5404	ACAACACCTCCTCCTGCTG	CAGCAGGAGGAGGTGTTGT
5405	CAACACCTCCTCCTGCTGC	GCAGCAGGAGGAGGTGTTG
5406	AACACCTCCTCCTGCTGCT	AGCAGCAGGAGGAGGTGTT
5407	ACACCTCCTCCTGCTGCTC	GAGCAGCAGGAGGAGGTGT
5408	CACCTCCTCCTGCTGCTCA	TGAGCAGCAGGAGGAGGTG
5409	ACCTCCTCCTGCTGCTCAC	GTGAGCAGCAGGAGGAGGT
5410	CCTCCTCCTGCTGCTCACT	AGTGAGCAGCAGGAGGAGG
5411	CTCCTCCTGCTGCTCACTC	GAGTGAGCAGCAGGAGGAG
5412	TCCTCCTGCTGCTCACTCC	GGAGTGAGCAGCAGGAGGA
5413	CCTCCTGCTGCTCACTCCC	GGGAGTGAGCAGCAGGAGG
5414	CTCCTGCTGCTCACTCCCG	CGGGAGTGAGCAGCAGGAG
5415	TCCTGCTGCTCACTCCCGC	GCGGGAGTGAGCAGCAGGA
5416	CCTGCTGCTCACTCCCGCT	AGCGGGAGTGAGCAGCAGG
5417	CTGCTGCTCACTCCCGCTG	CAGCGGGAGTGAGCAGCAG
5418	TGCTGCTCACTCCCGCTGA	TCAGCGGGAGTGAGCAGCA
5419	GCTGCTCACTCCCGCTGAG	CTCAGCGGGAGTGAGCAGC
5420	CTGCTCACTCCCGCTGAGC	GCTCAGCGGGAGTGAGCAG
5421	TGCTCACTCCCGCTGAGCC	GGCTCAGCGGGAGTGAGCA
5422	GCTCACTCCCGCTGAGCCC	GGGCTCAGCGGGAGTGAGC
5423	CTCACTCCCGCTGAGCCCA	TGGGCTCAGCGGGAGTGAG
5424	TCACTCCCGCTGAGCCCAC	GTGGGCTCAGCGGGAGTGA
5425	CACTCCCGCTGAGCCCACT	AGTGGGCTCAGCGGGAGTG
5426	ACTCCCGCTGAGCCCACTC	GAGTGGGCTCAGCGGGAGT
5427	CTCCCGCTGAGCCCACTCT	AGAGTGGGCTCAGCGGGAG
5428	TCCCGCTGAGCCCACTCTA	TAGAGTGGGCTCAGCGGGA
5429	CCCGCTGAGCCCACTCTAC	GTAGAGTGGGCTCAGCGGG
5430	CCGCTGAGCCCACTCTACT	AGTAGAGTGGGCTCAGCGG
5431	CGCTGAGCCCACTCTACTG	CAGTAGAGTGGGCTCAGCG
5432	GCTGAGCCCACTCTACTGC	GCAGTAGAGTGGGCTCAGC
5433	CTGAGCCCACTCTACTGCC	GGCAGTAGAGTGGGCTCAG
5434	TGAGCCCACTCTACTGCCC	GGGCAGTAGAGTGGGCTCA
5435	GAGCCCACTCTACTGCCCC	GGGGCAGTAGAGTGGGCTC
5436	AGCCCACTCTACTGCCCCA	TGGGGCAGTAGAGTGGGCT
5437	GCCCACTCTACTGCCCCAG	CTGGGGCAGTAGAGTGGGC
5438	CCCACTCTACTGCCCCAGC	GCTGGGGCAGTAGAGTGGG
5439	CCACTCTACTGCCCCAGCT	AGCTGGGGCAGTAGAGTGG
5440	CACTCTACTGCCCCAGCTC	GAGCTGGGGCAGTAGAGTG
5441	ACTCTACTGCCCCAGCTCC	GGAGCTGGGGCAGTAGAGT
5442	CTCTACTGCCCCAGCTCCG	CGGAGCTGGGGCAGTAGAG
5443	TCTACTGCCCCAGCTCCGT	ACGGAGCTGGGGCAGTAGA
5444	CTACTGCCCCAGCTCCGTT	AACGGAGCTGGGGCAGTAG
5445	TACTGCCCCAGCTCCGTTT	AAACGGAGCTGGGGCAGTA
5446	ACTGCCCCAGCTCCGTTTC	GAAACGGAGCTGGGGCAGT
5447	CTGCCCCAGCTCCGTTTCT	AGAAACGGAGCTGGGGCAG
5448	TGCCCCAGCTCCGTTTCTA	TAGAAACGGAGCTGGGGCA
5449	GCCCCAGCTCCGTTTCTAC	GTAGAAACGGAGCTGGGGC
5450	CCCCAGCTCCGTTTCTACC	GGTAGAAACGGAGCTGGGG
5451	CCCAGCTCCGTTTCTACCA	TGGTAGAAACGGAGCTGGG
5452	CCAGCTCCGTTTCTACCAC	GTGGTAGAAACGGAGCTGG
5453	CAGCTCCGTTTCTACCACC	GGTGGTAGAAACGGAGCTG
5454	AGCTCCGTTTCTACCACCG	CGGTGGTAGAAACGGAGCT
5455	GCTCCGTTTCTACCACCGC	GCGGTGGTAGAAACGGAGC
5456	CTCCGTTTCTACCACCGCA	TGCGGTGGTAGAAACGGAG
5457	TCCGTTTCTACCACCGCAT	ATGCGGTGGTAGAAACGGA
5458	CCGTTTCTACCACCGCATC	GATGCGGTGGTAGAAACGG
5459	CGTTTCTACCACCGCATCC	GGATGCGGTGGTAGAAACG
5460	GTTTCTACCACCGCATCCT	AGGATGCGGTGGTAGAAAC
5461	TTTCTACCACCGCATCCTC	GAGGATGCGGTGGTAGAAA
5462	TTCTACCACCGCATCCTCA	TGAGGATGCGGTGGTAGAA
5463	TCTACCACCGCATCCTCAC	GTGAGGATGCGGTGGTAGA
5464	CTACCACCGCATCCTCACT	AGTGAGGATGCGGTGGTAG
5465	TACCACCGCATCCTCACTG	CAGTGAGGATGCGGTGGTA
5466	ACCACCGCATCCTCACTGG	CCAGTGAGGATGCGGTGGT
5467	CCACCGCATCCTCACTGGG	CCCAGTGAGGATGCGGTGG
5468	CACCGCATCCTCACTGGGC	GCCCAGTGAGGATGCGGTG
5469	ACCGCATCCTCACTGGGCT	AGCCCAGTGAGGATGCGGT
5470	CCGCATCCTCACTGGGCTC	GAGCCCAGTGAGGATGCGG
5471	CGCATCCTCACTGGGCTCA	TGAGCCCAGTGAGGATGCG
5472	GCATCCTCACTGGGCTCAC	GTGAGCCCAGTGAGGATGC
5473	CATCCTCACTGGGCTCACT	AGTGAGCCCAGTGAGGATG
5474	ATCCTCACTGGGCTCACTG	CAGTGAGCCCAGTGAGGAT
5475	TCCTCACTGGGCTCACTGC	GCAGTGAGCCCAGTGAGGA
5476	CCTCACTGGGCTCACTGCA	TGCAGTGAGCCCAGTGAGG
5477	CTCACTGGGCTCACTGCAG	CTGCAGTGAGCCCAGTGAG
5478	TCACTGGGCTCACTGCAGG	CCTGCAGTGAGCCCAGTGA
5479	CACTGGGCTCACTGCAGGC	GCCTGCAGTGAGCCCAGTG
5480	ACTGGGCTCACTGCAGGCA	TGCCTGCAGTGAGCCCAGT
5481	CTGGGCTCACTGCAGGCAT	ATGCCTGCAGTGAGCCCAG
5482	TGGGCTCACTGCAGGCATG	CATGCCTGCAGTGAGCCCA
5483	GGGCTCACTGCAGGCATGC	GCATGCCTGCAGTGAGCCC
5484	GGCTCACTGCAGGCATGCT	AGCATGCCTGCAGTGAGCC
5485	GCTCACTGCAGGCATGCTG	CAGCATGCCTGCAGTGAGC
5486	CTCACTGCAGGCATGCTGA	TCAGCATGCCTGCAGTGAG
5487	TCACTGCAGGCATGCTGAA	TTCAGCATGCCTGCAGTGA
5488	CACTGCAGGCATGCTGAAC	GTTCAGCATGCCTGCAGTG
5489	ACTGCAGGCATGCTGAACA	TGTTCAGCATGCCTGCAGT
5490	CTGCAGGCATGCTGAACAA	TTGTTCAGCATGCCTGCAG
5491	TGCAGGCATGCTGAACAAG	CTTGTTCAGCATGCCTGCA
5492	GCAGGCATGCTGAACAAGG	CCTTGTTCAGCATGCCTGC
5493	CAGGCATGCTGAACAAGGG	CCCTTGTTCAGCATGCCTG
5494	AGGCATGCTGAACAAGGGG	CCCCTTGTTCAGCATGCCT
5495	GGCATGCTGAACAAGGGGC	GCCCCTTGTTCAGCATGCC
5496	GCATGCTGAACAAGGGGCC	GGCCCCTTGTTCAGCATGC
5497	CATGCTGAACAAGGGGCCT	AGGCCCCTTGTTCAGCATG
5498	ATGCTGAACAAGGGGCCTC	GAGGCCCCTTGTTCAGCAT
5499	TGCTGAACAAGGGGCCTCC	GGAGGCCCCTTGTTCAGCA
5500	GCTGAACAAGGGGCCTCCA	TGGAGGCCCCTTGTTCAGC
5501	CTGAACAAGGGGCCTCCAA	TTGGAGGCCCCTTGTTCAG
5502	TGAACAAGGGGCCTCCAAC	GTTGGAGGCCCCTTGTTCA
5503	GAACAAGGGGCCTCCAACC	GGTTGGAGGCCCCTTGTTC
5504	AACAAGGGGCCTCCAACCT	AGGTTGGAGGCCCCTTGTT
5505	ACAAGGGGCCTCCAACCTT	AAGGTTGGAGGCCCCTTGT
5506	CAAGGGGCCTCCAACCTTC	GAAGGTTGGAGGCCCCTTG
5507	AAGGGGCCTCCAACCTTCT	AGAAGGTTGGAGGCCCCTT
5508	AGGGGCCTCCAACCTTCTG	CAGAAGGTTGGAGGCCCCT
5509	GGGGCCTCCAACCTTCTGC	GCAGAAGGTTGGAGGCCCC
5510	GGGCCTCCAACCTTCTGCC	GGCAGAAGGTTGGAGGCCC
5511	GGCCTCCAACCTTCTGCCC	GGGCAGAAGGTTGGAGGCC
5512	GCCTCCAACCTTCTGCCCT	AGGGCAGAAGGTTGGAGGC
5513	CCTCCAACCTTCTGCCCTC	GAGGGCAGAAGGTTGGAGG
5514	CTCCAACCTTCTGCCCTCC	GGAGGGCAGAAGGTTGGAG
5515	TCCAACCTTCTGCCCTCCT	AGGAGGGCAGAAGGTTGGA
5516	CCAACCTTCTGCCCTCCTG	CAGGAGGGCAGAAGGTTGG
5517	CAACCTTCTGCCCTCCTGC	GCAGGAGGGCAGAAGGTTG
5518	AACCTTCTGCCCTCCTGCC	GGCAGGAGGGCAGAAGGTT
5519	ACCTTCTGCCCTCCTGCCA	TGGCAGGAGGGCAGAAGGT
5520	CCTTCTGCCCTCCTGCCAA	TTGGCAGGAGGGCAGAAGG
5521	CTTCTGCCCTCCTGCCAAA	TTTGGCAGGAGGGCAGAAG
5522	TTCTGCCCTCCTGCCAAAA	TTTTGGCAGGAGGGCAGAA
5523	TCTGCCCTCCTGCCAAAAG	CTTTTGGCAGGAGGGCAGA
5524	CTGCCCTCCTGCCAAAAGA	TCTTTTGGCAGGAGGGCAG
5525	TGCCCTCCTGCCAAAAGAT	ATCTTTTGGCAGGAGGGCA
5526	GCCCTCCTGCCAAAAGATC	GATCTTTTGGCAGGAGGGC
5527	CCCTCCTGCCAAAAGATCT	AGATCTTTTGGCAGGAGGG
5528	CCTCCTGCCAAAAGATCTG	CAGATCTTTTGGCAGGAGG
5529	CTCCTGCCAAAAGATCTGG	CCAGATCTTTTGGCAGGAG
5530	TCCTGCCAAAAGATCTGGG	CCCAGATCTTTTGGCAGGA
5531	CCTGCCAAAAGATCTGGGG	CCCCAGATCTTTTGGCAGG
5532	CTGCCAAAAGATCTGGGGA	TCCCCAGATCTTTTGGCAG
5533	TGCCAAAAGATCTGGGGAG	CTCCCCAGATCTTTTGGCA
5534	GCCAAAAGATCTGGGGAGT	ACTCCCCAGATCTTTTGGC
5535	CCAAAAGATCTGGGGAGTG	CACTCCCCAGATCTTTTGG
5536	CAAAAGATCTGGGGAGTGT	ACACTCCCCAGATCTTTTG
5537	AAAAGATCTGGGGAGTGTG	CACACTCCCCAGATCTTTT
5538	AAAGATCTGGGGAGTGTGA	TCACACTCCCCAGATCTTT
5539	AAGATCTGGGGAGTGTGAG	CTCACACTCCCCAGATCTT
5540	AGATCTGGGGAGTGTGAGG	CCTCACACTCCCCAGATCT
5541	GATCTGGGGAGTGTGAGGA	TCCTCACACTCCCCAGATC
5542	ATCTGGGGAGTGTGAGGAG	CTCCTCACACTCCCCAGAT
5543	TCTGGGGAGTGTGAGGAGA	TCTCCTCACACTCCCCAGA
5544	CTGGGGAGTGTGAGGAGAG	CTCTCCTCACACTCCCCAG
5545	TGGGGAGTGTGAGGAGAGG	CCTCTCCTCACACTCCCCA
5546	GGGGAGTGTGAGGAGAGGG	CCCTCTCCTCACACTCCCC
5547	GGGAGTGTGAGGAGAGGGT	ACCCTCTCCTCACACTCCC
5548	GGAGTGTGAGGAGAGGGTG	CACCCTCTCCTCACACTCC
5549	GAGTGTGAGGAGAGGGTGG	CCACCCTCTCCTCACACTC
5550	AGTGTGAGGAGAGGGTGGC	GCCACCCTCTCCTCACACT
5551	GTGTGAGGAGAGGGTGGCA	TGCCACCCTCTCCTCACAC
5552	TGTGAGGAGAGGGTGGCAT	ATGCCACCCTCTCCTCACA
5553	GTGAGGAGAGGGTGGCATC	GATGCCACCCTCTCCTCAC
5554	TGAGGAGAGGGTGGCATCA	TGATGCCACCCTCTCCTCA
5555	GAGGAGAGGGTGGCATCAG	CTGATGCCACCCTCTCCTC
5556	AGGAGAGGGTGGCATCAGG	CCTGATGCCACCCTCTCCT
5557	GGAGAGGGTGGCATCAGGA	TCCTGATGCCACCCTCTCC
5558	GAGAGGGTGGCATCAGGAG	CTCCTGATGCCACCCTCTC
5559	AGAGGGTGGCATCAGGAGC	GCTCCTGATGCCACCCTCT
5560	GAGGGTGGCATCAGGAGCT	AGCTCCTGATGCCACCCTC
5561	AGGGTGGCATCAGGAGCTG	CAGCTCCTGATGCCACCCT
5562	GGGTGGCATCAGGAGCTGC	GCAGCTCCTGATGCCACCC
5563	GGTGGCATCAGGAGCTGCT	AGCAGCTCCTGATGCCACC
5564	GTGGCATCAGGAGCTGCTC	GAGCAGCTCCTGATGCCAC
5565	TGGCATCAGGAGCTGCTCA	TGAGCAGCTCCTGATGCCA
5566	GGCATCAGGAGCTGCTCAG	CTGAGCAGCTCCTGATGCC
5567	GCATCAGGAGCTGCTCAGG	CCTGAGCAGCTCCTGATGC
5568	CATCAGGAGCTGCTCAGGC	GCCTGAGCAGCTCCTGATG
5569	ATCAGGAGCTGCTCAGGCT	AGCCTGAGCAGCTCCTGAT
5570	TCAGGAGCTGCTCAGGCTT	AAGCCTGAGCAGCTCCTGA
5571	CAGGAGCTGCTCAGGCTTG	CAAGCCTGAGCAGCTCCTG
5572	AGGAGCTGCTCAGGCTTGG	CCAAGCCTGAGCAGCTCCT
5573	GGAGCTGCTCAGGCTTGGC	GCCAAGCCTGAGCAGCTCC
5574	GAGCTGCTCAGGCTTGGCG	CGCCAAGCCTGAGCAGCTC
5575	AGCTGCTCAGGCTTGGCGG	CCGCCAAGCCTGAGCAGCT
5576	GCTGCTCAGGCTTGGCGGA	TCCGCCAAGCCTGAGCAGC
5577	CTGCTCAGGCTTGGCGGAG	CTCCGCCAAGCCTGAGCAG
5578	TGCTCAGGCTTGGCGGAGG	CCTCCGCCAAGCCTGAGCA
5579	GCTCAGGCTTGGCGGAGGG	CCCTCCGCCAAGCCTGAGC
5580	CTCAGGCTTGGCGGAGGGA	TCCCTCCGCCAAGCCTGAG
5581	TCAGGCTTGGCGGAGGGAG	CTCCCTCCGCCAAGCCTGA
5582	CAGGCTTGGCGGAGGGAGC	GCTCCCTCCGCCAAGCCTG
5583	AGGCTTGGCGGAGGGAGCG	CGCTCCCTCCGCCAAGCCT
5584	GGCTTGGCGGAGGGAGCGG	CCGCTCCCTCCGCCAAGCC
5585	GCTTGGCGGAGGGAGCGGC	GCCGCTCCCTCCGCCAAGC
5586	CTTGGCGGAGGGAGCGGCA	TGCCGCTCCCTCCGCCAAG
5587	TTGGCGGAGGGAGCGGCAT	ATGCCGCTCCCTCCGCCAA
5588	TGGCGGAGGGAGCGGCATG	CATGCCGCTCCCTCCGCCA
5589	GGCGGAGGGAGCGGCATGG	CCATGCCGCTCCCTCCGCC
5590	GCGGAGGGAGCGGCATGGG	CCCATGCCGCTCCCTCCGC
5591	CGGAGGGAGCGGCATGGGC	GCCCATGCCGCTCCCTCCG
5592	GGAGGGAGCGGCATGGGCG	CGCCCATGCCGCTCCCTCC
5593	GAGGGAGCGGCATGGGCGA	TCGCCCATGCCGCTCCCTC
5594	AGGGAGCGGCATGGGCGAT	ATCGCCCATGCCGCTCCCT
5595	GGGAGCGGCATGGGCGATG	CATCGCCCATGCCGCTCCC
5596	GGAGCGGCATGGGCGATGT	ACATCGCCCATGCCGCTCC
5597	GAGCGGCATGGGCGATGTC	GACATCGCCCATGCCGCTC
5598	AGCGGCATGGGCGATGTCA	TGACATCGCCCATGCCGCT
5599	GCGGCATGGGCGATGTCAC	GTGACATCGCCCATGCCGC
5600	CGGCATGGGCGATGTCACT	AGTGACATCGCCCATGCCG
5601	GGCATGGGCGATGTCACTC	GAGTGACATCGCCCATGCC
5602	GCATGGGCGATGTCACTCA	TGAGTGACATCGCCCATGC
5603	CATGGGCGATGTCACTCAG	CTGAGTGACATCGCCCATG
5604	ATGGGCGATGTCACTCAGC	GCTGAGTGACATCGCCCAT
5605	TGGGCGATGTCACTCAGCC	GGCTGAGTGACATCGCCCA
5606	GGGCGATGTCACTCAGCCC	GGGCTGAGTGACATCGCCC
5607	GGCGATGTCACTCAGCCCC	GGGGCTGAGTGACATCGCC
5608	GCGATGTCACTCAGCCCCT	AGGGGCTGAGTGACATCGC
5609	CGATGTCACTCAGCCCCTT	AAGGGGCTGAGTGACATCG
5610	GATGTCACTCAGCCCCTTC	GAAGGGGCTGAGTGACATC
5611	ATGTCACTCAGCCCCTTCC	GGAAGGGGCTGAGTGACAT
5612	TGTCACTCAGCCCCTTCCC	GGGAAGGGGCTGAGTGACA
5613	GTCACTCAGCCCCTTCCCG	CGGGAAGGGGCTGAGTGAC
5614	TCACTCAGCCCCTTCCCGG	CCGGGAAGGGGCTGAGTGA
5615	CACTCAGCCCCTTCCCGGT	ACCGGGAAGGGGCTGAGTG
5616	ACTCAGCCCCTTCCCGGTC	GACCGGGAAGGGGCTGAGT
5617	CTCAGCCCCTTCCCGGTCC	GGACCGGGAAGGGGCTGAG
5618	TCAGCCCCTTCCCGGTCCG	CGGACCGGGAAGGGGCTGA
5619	CAGCCCCTTCCCGGTCCGC	GCGGACCGGGAAGGGGCTG
5620	AGCCCCTTCCCGGTCCGCC	GGCGGACCGGGAAGGGGCT
5621	GCCCCTTCCCGGTCCGCCC	GGGCGGACCGGGAAGGGGC
5622	CCCCTTCCCGGTCCGCCCG	CGGGCGGACCGGGAAGGGG
5623	CCCTTCCCGGTCCGCCCGC	GCGGGCGGACCGGGAAGGG
5624	CCTTCCCGGTCCGCCCGCT	AGCGGGCGGACCGGGAAGG
5625	CTTCCCGGTCCGCCCGCTT	AAGCGGGCGGACCGGGAAG
5626	TTCCCGGTCCGCCCGCTTC	GAAGCGGGCGGACCGGGAA
5627	TCCCGGTCCGCCCGCTTCC	GGAAGCGGGCGGACCGGGA
5628	CCCGGTCCGCCCGCTTCCC	GGGAAGCGGGCGGACCGGG
5629	CCGGTCCGCCCGCTTCCCT	AGGGAAGCGGGCGGACCGG
5630	CGGTCCGCCCGCTTCCCTC	GAGGGAAGCGGGCGGACCG
5631	GGTCCGCCCGCTTCCCTCC	GGAGGGAAGCGGGCGGACC
5632	GTCCGCCCGCTTCCCTCCT	AGGAGGGAAGCGGGCGGAC
5633	TCCGCCCGCTTCCCTCCTT	AAGGAGGGAAGCGGGCGGA
5634	CCGCCCGCTTCCCTCCTTC	GAAGGAGGGAAGCGGGCGG
5635	CGCCCGCTTCCCTCCTTCA	TGAAGGAGGGAAGCGGGCG
5636	GCCCGCTTCCCTCCTTCAT	ATGAAGGAGGGAAGCGGGC
5637	CCCGCTTCCCTCCTTCATG	CATGAAGGAGGGAAGCGGG
5638	CCGCTTCCCTCCTTCATGA	TCATGAAGGAGGGAAGCGG
5639	CGCTTCCCTCCTTCATGAT	ATCATGAAGGAGGGAAGCG
5640	GCTTCCCTCCTTCATGATT	AATCATGAAGGAGGGAAGC
5641	CTTCCCTCCTTCATGATTT	AAATCATGAAGGAGGGAAG
5642	TTCCCTCCTTCATGATTTC	GAAATCATGAAGGAGGGAA
5643	TCCCTCCTTCATGATTTCC	GGAAATCATGAAGGAGGGA
5644	CCCTCCTTCATGATTTCCA	TGGAAATCATGAAGGAGGG
5645	CCTCCTTCATGATTTCCAT	ATGGAAATCATGAAGGAGG
5646	CTCCTTCATGATTTCCATT	AATGGAAATCATGAAGGAG
5647	TCCTTCATGATTTCCATTA	TAATGGAAATCATGAAGGA
5648	CCTTCATGATTTCCATTAA	TTAATGGAAATCATGAAGG
5649	CTTCATGATTTCCATTAAA	TTTAATGGAAATCATGAAG
5650	TTCATGATTTCCATTAAAG	CTTTAATGGAAATCATGAA
5651	TCATGATTTCCATTAAAGT	ACTTTAATGGAAATCATGA
5652	CATGATTTCCATTAAAGTC	GACTTTAATGGAAATCATG
5653	ATGATTTCCATTAAAGTCT	AGACTTTAATGGAAATCAT
5654	TGATTTCCATTAAAGTCTG	CAGACTTTAATGGAAATCA
5655	GATTTCCATTAAAGTCTGT	ACAGACTTTAATGGAAATC
5656	ATTTCCATTAAAGTCTGTT	AACAGACTTTAATGGAAAT
5657	TTTCCATTAAAGTCTGTTG	CAACAGACTTTAATGGAAA
5658	TTCCATTAAAGTCTGTTGT	ACAACAGACTTTAATGGAA
5659	TCCATTAAAGTCTGTTGTT	AACAACAGACTTTAATGGA
5660	CCATTAAAGTCTGTTGTTT	AAACAACAGACTTTAATGG
5661	CATTAAAGTCTGTTGTTTT	AAAACAACAGACTTTAATG
5662	ATTAAAGTCTGTTGTTTTG	CAAAACAACAGACTTTAAT
5663	TTAAAGTCTGTTGTTTTGT	ACAAAACAACAGACTTTAA
5664	TAAAGTCTGTTGTTTTGTG	CACAAAACAACAGACTTTA

TABLE 2
Human and Mouse Hairless Polymorphisms
	mRNA	Accession	Postion
Gene	(bp)	number	(nt)	From/To	Comments
Human	5699	NM_005144	867	C/A	Homo sapiens
Hairless			1330	T/G	hairless
			1677	C/T	homolog
			1686	C/T	(mouse) (HR),
			2437	C/A	transcript
			2491	G/A	variant 1,
			2671	G/A	mRNA
			2672	C/T
			2786	T/C
			3058	T/C
			3064	A/G
			3208	C/T
			3253	G/A
			3340	G/A
			3695	C/T
			3812	A/T
			3851	C/T
			3854	C/T
			4545	A/G
			4715	C/G
			4820	C/A
Mouse	5599	NM_021877	402	A/G	Mus musculus
hairless			535	C/A	hairless (hr),
			1603	G/A	mRNA
			1681	A/G
			1895	C/T
			2251	G/A
			2482	T/C
			2569	T/C
			2917	T/C
			3232	C/T
			3371	A/T
			3610	C/A
			4065	T/G

TABLE 3
Exemplary siRNA target sequences in
mammalian hairless mRNAs (shown as
cDNA sequences)
	Start	Sequence	Region
	Mouse (Mus musculus) hairless (hr), mRNA,
	NM_021877
	2023	GCAGGAGACACCGGAGACAATCATA	ORF
		(SEQ ID NO: 11373)
	2495	GGACTCTTCAACACCCACTGGAGAT	ORF
		(SEQ ID NO: 11374)
	2713	CCAAGTCTGGGCCAAGTTTGACATT	ORF
		(SEQ ID NO: 11375)
	2831	CCACAACCTTCCTGCAATGGAGATT	ORF
		(SEQ ID NO: 11376)
	2844	GCAATGGAGATTCCAATCGGACCAA	ORF
		(SEQ ID NO: 11377)
	3042	CCAGTGATGACCGCATTACCAACAT	ORF
		(SEQ ID NO: 11378)
	3085	GCAGGTAGTAGAACGGAAGATCCAA	ORF
		(SEQ ID NO: 11379)
	3750	CCTGGTATCGAGCACAGAAAGATTT	ORF
		(SEQ ID NO: 11380)
	4068	GCACAATCAGTGTCACTCAGCACTT	ORF
		(SEQ ID NO: 11381)
	Homo sapiens hairless homolog (mouse) (HR),
	transcript variant 1, mRNA, NM_005144
	2151	GCGGAACCTGGGTTGTTTGGCTTAA	ORF
		(SEQ ID NO: 11382)
	2831	GGACACATCGATAGGGAACAAGGAT	ORF
		(SEQ ID NO: 11383)
	3626	CCCAACTCCACAACCTTCCTGCAAT	ORF
		(SEQ ID NO: 11384)
	3796	GCCATGAGCGAATACACATGGCCTT	ORF
		(SEQ ID NO: 11385)
	4092	CCTGTGTTGGTGTCAGGGATCCAAA	ORF
		(SEQ ID NO: 11386)
	Rat (Rattus norvegicus) hairless (hr) mRNA,
	NM-024364
	913	CCAAGATTCTAGAGCGAGCTCCCTT	ORF
		(SEQ ID NO: 11387)
	2045	GGATTCCTGTGCCACTTCTGAGGAA	ORF
		(SEQ ID NO: 11388)
	2601	CCACAACTTTCCTGCAATGGAGATT	ORF
		(SEQ ID NO: 11389)
	2614	GCAATGGAGATTCCAATCGGACCAA	ORF
		(SEQ ID NO: 11390)
	2729	GCTGCTAGCCTCTACAGCTGTCAAA	ORF
		(SEQ ID NO: 11391)
	2765	GCATGAGCGGATTCACATGGCCTTT	ORF
		(SEQ ID NO: 11392)
	2812	CCAGTGATGACCGCATTACCAACAT	ORF
		(SEQ ID NO: 11393)
	2855	GCAGGTAGTAGAACGGAAGATCCAA	ORF
		(SEQ ID NO: 11394)
	3520	CCTGGTACCGAGCACAGAAAGATTT	ORF
		(SEQ ID NO: 11395)
	3838	GCACAATCAGTGTCACTCAGCACTT	ORF
		(SEQ ID NO: 11396)
	Monkey (Macaca mulatto) hairless mRNA,
	complete cds, AF_361864
	1152	GCACTCGGAGCAGTTTGAATGTCCA	ORF
		(SEQ ID NO: 11397)
	1344	GGACACATCGATAGGGAACAAGGAG	ORF
		(SEQ ID NO: 11398)
	2025	GCACCAGGTCTGGGTCAAGTTTGAT	ORF
		(SEQ ID NO: 11399)
	2172	CCACAGGACCAAGAGCATCAAAGAG	ORF
		(SEQ ID NO: 113400)
	2605	CCTGTGTTGGTGTCAGGGATCCAAA	ORF
		(SEQ ID NO: 11401)
	Pig (Sus scrofa) hairless mRNA, partical
	cds, AY279972
	490	CAGATATGGGCAGCCTATGGTGTGA	ORF
		(SEQ ID NO: 11402)
	918	CCTGGTAAGCACAGTGAGCATCACT	ORF
		(SEQ ID NO: 11403)
	921	GGTAAGCACAGTGAGCATCACTCAG	ORF
		(SEQ ID NO: 11404)
	926	GCACAGTGAGCATCACTCAGCACTT	ORF
		(SEQ ID NO: 11405)
	927	CACAGTGAGCATCACTCAGCACTTC	ORF
		(SEQ ID NO: 11406)
	Sheep (Ovis aries) hairless mRNA, partial
	cds, AY130969
	366	GGATCCTGAGCATAATGGTGGCCAT	ORF
		(SEQ ID NO: 11407)
	1140	GCTTACTCGACACTCTGAGCAGTTT	ORF
		(SEQ ID NO: 11408)
	1798	GGACTGTTCAATACCCACTGGAGAT	ORF
		(SEQ ID NO: 11409)
	1967	CCCAGTTTGTCTCCAGTCAGCCTTT	ORF
		(SEQ ID NO: 11410)
	2016	CCAGGTCTGGGTCAAGTTTGACATT	ORF
		(SEQ ID NO: 11411)

TABLE 4

Human hairless target/siRNA sequences
human hairless NM_005144


Loop: 475-615
Loop: 651-752
Loop: 951-1137
Loop: 1968-2183
Loop: 2348-2568
Loop: 2769-2806
Loop: 3024-3365
Loop: 3069-3277
Loop: 4577-4698
Loop: 3605-3724
Loop: 4861-5079
Loop: 310-436
Loop: 1953-2248
Loop: 919-1265
Loop: 4286-4465
Loop: 2373-2555
Loop: 4853-5284
Loop: 1916-2288
Loop: 2739-2863
Loop: 4874-5043
Loop: 3047-3318
Loop: 959-1123
Loop: 4477-4534
Loop: 871-1302
Loop: 4325-4459
Loop: 4913-5029
Loop: 940-1166
Loop: 1946-2277
Loop: 4086-4199
Loop: 5093-5247

TABLE 5

Mouse hairless target/siRNA sequences
mouse hairless NM_021877


Loop: 318-523
Loop: 2422-2459
Loop: 1870-1913
Loop: 5010-5089
Loop: 3614-3736
Loop: 20-23
Loop: 1048-1390
Loop: 1122-1304
Loop: 3434-3550
Loop: 3257-3337
Loop: 4272-4504
Loop: 3009-3024
Loop: 4879-4967
Loop: 668-845
Loop: 4050-4222
Loop: 1702-1800
Loop: 3364-3567
Loop: 1015-1029
Loop: 4730-4780
Loop: 1712-1792
Loop: 4540-4566
Loop: 4070-4135
Loop: 1220-1260
Loop: 3579-3701
Loop: 445-459
Loop: 3491-3516
Loop: 205-238
Loop: 1691-1926
Loop: 2320-2337
Loop: 896-951
Loop: 2212-2244
Loop: 5156-5179
Loop: 2850-3948
Loop: 1141-1201
Loop: 2588-2648
Loop: 403-518
Loop: 3370-3407
Loop: 412-510
Loop: 4517-4594
Loop: 659-871
Loop: 1087-1103
Loop: 1600-1624
Loop: 4389-4461
Loop: 3423-3561
Loop: 713-812
Loop: 176-302
Loop: 1073-1336
Loop: 675-837
Loop: 4395-4417
Loop: 1082-1316
Loop: 4152-4215
Loop: 2877-2944

Claims

1. A method of removing hair from an area of a human, comprising:

(A) first synchronizing hair growth cycles for hair follicles in said area, wherein said synchronization is accomplished by:

(i) twice pulling the hair from said follicles; or

(ii) administering a follicle growth inducer to said area; and

(B) subsequently applying to said area a double stranded nucleic acid molecule comprising:

(i) a sense sequence corresponding to 19-29 contiguous nucleotides of SEQ ID NO: 11412; and

(ii) an antisense sequence complementary thereto, wherein said double stranded nucleic acid molecule inhibits expression of human hairless protein, whereby hair growth in said area is inhibited.

2. The method of claim 1, wherein inhibition of hair growth in said area persists at least one month.

3. The method of claim 1, wherein said double stranded nucleic acid comprises at least one 3′-overhang.

4. The method of claim 3, wherein said 3′-overhang is a 2- or 3′-base overhang.

5. The method of claim 3, wherein said 3′-overhang comprises at least one deoxynucleotide.

6. The method of claim 1, wherein at least one strand of said double stranded nucleic acid comprises at least one nucleotide analog or internucleotidic linkage different from unmodified RNA.

7. The method of claim 1, wherein said sense sequence comprises SEQ ID NO:11329.

8. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 19 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

9. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 20 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

10. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 21 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

11. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 22 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

12. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 23 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

13. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 24 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

14. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 25 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

15. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 26 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

16. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 27 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

17. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 28 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

18. A method for removing hair from an area of a mammal, comprising:

(A) synchronizing hair growth cycles for hair follicles in said area, wherein said synchronization is accomplished by:

(i) twice pulling the hair from said follicles; or

(ii) administering a follicle growth inducer to said area; and

(B) subsequently applying to said area a double stranded nucleic acid molecule comprising:

(i) a sense sequence corresponding to 19-29 contiguous nucleotides of SEQ ID NO: 11412 and

(ii) an antisense sequence complementary thereto, wherein said double stranded nucleic acid molecule inhibits hairless mRNA translation.

19. The method of claim 18, wherein said mammal is a human.

20. The method of claim 18, wherein inhibition of hair growth in said area persists at least one month.

21. The method of claim 18, wherein said double stranded nucleic acid comprises at least one 3′-overhang.

22. The method of claim 21 wherein said 3′-overhang is a 2- or 3′-base overhang.

23. The method of claim 22 wherein said 3′-overhang comprises at least one deoxynucleotide.

24. The method of claim 18, wherein at least one strand of said double stranded nucleic acid comprises at least one nucleotide analog or internucleotidic linkage different from unmodified RNA.

25. The method of claim 18, wherein said sense sequence comprises SEQ ID NO:11329.

26. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 19 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

27. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 20 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

28. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 21 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

29. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 22 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

30. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 23 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

31. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 24 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

32. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 25 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

33. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 26 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

34. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 27 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

35. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 28 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

36. A method of inhibiting expression of hairless protein in an area of a mammal, comprising:

(A) first synchronizing hair growth cycles for hair follicles in said area, wherein said synchronization is accomplished by:

(i) twice pulling the hair from said follicles; or

(ii) administering a follicle growth inducer to said area; and

(B) subsequently applying to said area a double stranded nucleic acid molecule comprising:

(i) a sense sequence corresponding to 19-29 contiguous nucleotides of SEQ ID NO: 11412; and

(ii) an antisense sequence complementary thereto.

37. A method for treating a human desirous of losing hair in an area, comprising:

(A) first synchronizing hair growth cycles for hair follicles in said area, wherein said synchronization is accomplished by:

(i) twice pulling the hair from said follicles; or

(ii) administering a follicle growth inducer to said area; and

(B) subsequently applying to said area a double stranded nucleic acid molecule comprising:

(i) a sense sequence corresponding to 19-29 contiguous nucleotides of SEQ ID NO: 11412; and

(ii) an antisense sequence complementary thereto.